Podcasts about regulatory t

Regulatory T cells in the spinal meninges release endogenous opioids in a sex-specific manner, new work shows.

Timestamps:      00:00- Introduction  00:41- Health benefits of yoga and mindfulness   02:34- The potential of AI in hematology  04:23- Transfusion dependence in myelodysplastic syndromes  08:13- The fascinating field of apheresis  10:56- How to provide high-quality, affordable healthcare?  15:44- Regulatory T cells in hematologic malignancies  19:55- CAR T clinical trials: regulatory insights  22:57- EBMT initiatives  30:06- Latest breakthroughs in amyloidosis   34:50- Reducing patient fear through education 

We love to hear from our listeners. Send us a message.In this episode, Host Erin Harris sits down with Dr. Simrit Parmar, Founder of Cellenkos, to explore how the company is pioneering umbilical cord blood-derived Regulatory T cell (Treg) cell therapies for autoimmune and inflammatory diseases. Dr. Parmar shares the vision behind Cellenkos, the advantages of cord blood-derived Tregs over other sources, and how their CRANE technology platform enhances precision in targeting diseases. They also discuss key findings from their Phase 1b trial for CK0804, the challenges of scaling up off-the-shelf Treg therapies, and what's next for Cellenkos in 2025.Subscribe to the podcast!Apple | Spotify | YouTube

In this live Fertility Expert Q and A , I'm joined by Dr. Andrea Vidali. I had the honor of interviewing him about Pregmune, a platform for patients to receive a Reproductive Immunology work-up with him. We dove into the 6 categories that are part of a reproductive immunology work-up: HLA testing, NK activity, Systemic Inflammation, Thrombophilia, Regulatory T-cell, and Autoimmunity. It was so fascinating to learn from the best today. I hope you will listen in! Read the full show notes on Dr. Aimee's website. Pregmune's website. Subscribe to my YouTube channel for more fertility tips! Subscribe to the newsletter to get updates Do you have questions about IVF?Click here to join Dr. Aimee for The IVF Class. The next live class call is on Monday, December 16th, 2024 at 4pm PST (7pm EST), where Dr. Aimee will explain IVF and there will be time to ask her your questions live on Zoom. Dr. Aimee Eyvazzadeh is one of America's most well known fertility doctors. Her success rate at baby-making is what gives future parents hope when all hope is lost. She pioneered the TUSHY Method and BALLS Method to decrease your time to pregnancy. Learn more about the TUSHY Method and find a wealth of fertility resources at www.draimee.org.

On this episode of Healthcare Americana, host Christopher Habig, CEO of Freedom Healthworks, is joined by Howard Berman, CEO of Coya Therapeutics. Together, they discuss the complexities of neurodegenerative diseases and the groundbreaking work being done to combat them. Explore the profound impact of conditions like ALS, Alzheimer's, and Parkinson's, and discover Coya's pioneering approach that utilizes Regulatory T-cells (Tregs) to revolutionize therapy for neurodegeneration. Howard offers insights into Coya's imminent breakthroughs, explains the critical role the immune system plays in all neurodegenerative diseases, and touches upon the process of working with the government to bring new treatments to the public. He also shares the tragic circumstance that occurred, which ultimately lead him to the overnight decision of leaving his career in big pharma and propelling him on this mission-based path. Finally, Howard concludes with the high expectations he has for Coya in the next 12 months. Don't miss this enlightening discussion that sheds light on the pressing need to address the growing epidemic of neurodegenerative diseases.Follow Healthcare Americana:TwitterInstagramLinkedInMore on Freedom Healthworks & FreedomDocMore on Howard Berman & Coya TherapeuticsSubscribe at https://healthcareamericana.com/episodes/

Regulatory T cells target systemic inflammation and neuroinflammation, but when they fail to function properly, they can drive serious health conditions including neurodegenerative, metabolic, and autoimmune diseases. Coya Therapeutics is developing a pipeline of therapies designed to restore the ability of Tregs to modulate the immune system and reduce inflammation. The company's lead experimental therapy is a combination of two biologics designed to treat ALS by boosting anti-inflammatory Tregs while suppressing other immune cells that drive inflammation. We spoke to Howard Berman, chairman and CEO of Coya, about the role of inflammation in neurodegenerative conditions, Tregs, and the company's experimental therapy to treat ALS.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.25.525562v1?rss=1 Authors: de la Fuente, A. G., Dittmer, M., Heesbeen, E., de la Vega-Gallardo, N., White, J. A., Young, A., Mayne, K., Falconer, J., McMurran, C. E., Innayatulah, M., Tiwari, V., Penalva, R., Ingram, R. J., Dombrowski, Y., Fitzgerald, D. C. Abstract: Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis but its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as novel candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients and describe two novel mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this live Fertility Expert Q and A , I'm joined by Dr. Andrea Vidali. I had the honor of interviewing him about Pregmune, a platform for patients to receive a Reproductive Immunology work-up with him. We dove into the 6 categories that are part of a reproductive immunology work-up: HLA testing, NK activity, Systemic Inflammation, Thrombophilia, Regulatory T-cell, and Autoimmunity. It was so fascinating to learn from the best today. I hope you will listen in! Do you have questions about IVF?Click here to join Dr. Aimee for The IVF Class. The next live class call is on Monday, May 15, 2022 at 4pm PST, where Dr. Aimee will explain IVF and there will be time to ask her your questions live on Zoom.   Click to find The Egg Whisperer Show podcast on your favorite podcasting app.   Watch videos of Dr. Aimee answer Ask the Egg Whisperer Questions on YouTube.  Sign up for The Egg Whisperer newsletter to get updates  Dr. Aimee Eyvazzadeh is one of America's most well known fertility doctors. Her success rate at baby-making is what gives future parents hope when all hope is lost. She pioneered the TUSHY Method and BALLS Method to decrease your time to pregnancy. Learn more about the TUSHY Method and find a wealth of fertility resources at www.draimee.org.

Regulatory T cells, also known as Tregs, are specialized cells that are part of the immune system. As the name implies, they help regulate the body's immune natural immune response, among other functions According to some studies, the dysregulation of TRegs may play a role in several neurodegenerative disease. Coya Therapeutics is a Texas based biotech company working to utilize TReg therapies to treat these diseases – including ALS. Their ALS treatment completed a Phase 2a study in 2021, with results to be published later in 2022. They are also planning a phase 2b study later this year. Today, on Endpoints, we're joined by Dr. Adrian Hepner, Coya's Chief Medical Officer, to talk about how TRegs might be able to help people with ALS, give an update on the Phase the phase 2a study, and discuss plans for the next steps. Support the show: https://www.als.net/donate/ See omnystudio.com/listener for privacy information.

In this live Fertility Expert Q and A , I'm joined by Dr. Andrea Vidali. I had the honor of interviewing him about Pregmune, a platform for patients to receive a Reproductive Immunology work-up with him. We dove into the 6 categories that are part of a reproductive immunology work-up: HLA testing, NK activity, Systemic Inflammation, Thrombophilia, Regulatory T-cell, and Autoimmunity. It was so fascinating to learn from the best today. I hope you will listen in! Listen on Dr. Aimee's website Subscribe to my YouTube channel for more fertility tips!  Join Egg Whisperer School Subscribe to the newsletter to get updates  Dr. Aimee Eyvazzadeh is one of America's most well known fertility doctors. Her success rate at baby-making is what gives future parents hope when all hope is lost. She pioneered the TUSHY Method and BALLS Method to decrease your time to pregnancy. Learn more about the TUSHY Method and find a wealth of fertility resources at www.draimee.org.

Red and processed meat linked to increased risk of heart disease, study shows Oxford University, July 21, 2021 Globally, coronary heart diseases (caused by narrowed arteries that supply the heart with blood) claim nearly nine million lives each year1, the largest of any disease, and present a huge burden to health systems. Until now, it has been unclear whether eating meat increases the risk of heart disease, and if this varies for different kinds of meat. Researchers at the University of Oxford's Nuffield Department of Population Health have conducted the largest systematic review of the prospective evidence to date, including thirteen cohort studies involving over 1.4 million people. The study participants completed detailed dietary assessments, and their health was tracked for up to 30 years. The results are published today in Critical Reviews in Food Science and Nutrition. Overall, the evidence from the analysis indicated that: Each 50 g/day higher intake of processed meat (e.g. bacon, ham, and sausages) increased the risk of coronary heart disease by 18%. Each 50 g/day higher intake of unprocessed red meat (such as beef, lamb and pork) increased the risk of coronary heart disease by 9%. There was no clear link between eating poultry (such as chicken and turkey) and an increased risk of coronary heart disease. The findings may be because of the high content of saturated fat in red meat, and of sodium (salt) in processed meat. High intakes of saturated fat increase levels of harmful low-density lipoprotein (LDL) cholesterol, whilst excess salt consumption raises blood pressure. Both LDL cholesterol and high blood pressure are well-established risk factors for coronary heart disease. Previous work from the same research team has also indicated that even moderate intakes of red and processed meat are associated with increased risk of bowel cancer2. Dr. Keren Papier (Nuffield Department of Population Health), co-lead author of the study, said: "Red and processed meat have been consistently linked with bowel cancer and our findings suggest an additional role in heart disease. Therefore, current recommendations to limit red and processed meat consumption may also assist with the prevention of coronary heart disease." Dr. Anika Knüppel, from the Nuffield Department of Population Health and the other co-lead author of the study, added: "We know that meat production is a major contributor to greenhouse gas emissions and we need to reduce meat production and thereby consumption to benefit the environment. Our study shows that a reduction in red and processed meat intake would bring personal health benefits too." Currently in the UK, about 10 in 100 people would be expected to eventually die from coronary heart disease. Based on the findings from the present study and current red and processed meat intakes in the UK,4 if all these 100 people reduced their unprocessed red meat intake by three-quarters (for example from four times a week to one time a week), or if they stopped consuming processed meat altogether, deaths from coronary heart disease would decrease from 10 in 100 down to 9 in 100. The studies involved in this analysis were mostly based on white adults living in Europe or the U.S.. The research team say more data are needed to examine these associations in other populations, including East Asia and Africa.   C is for Vitamin C -- a key ingredient for immune cell function Harnessing the combined power of Vitamin C and TET proteins may give scientists a leg up in treating autoimmune diseases   La Jolla Institute for Immunology and Emory University, July 22, 2021 You can't make a banana split without bananas. And you can't generate stable regulatory T cells without Vitamin C or enzymes called TET proteins, it appears.  Regulatory T cells (Tregs) help control inflammation and autoimmunity in the body. Tregs are so important, in fact, that scientists are working to generate stable induced Tregs (iTregs) in vitro for use as treatments for autoimmune diseases as well as rejection to transplanted organs. Unfortunately, it has proven difficult to find the right molecular ingredients to induce stable iTregs. Now scientists at La Jolla Institute for Immunology and Emory University School of Medicine report that Vitamin C and TET proteins can work together to give Tregs their life-saving power.  "Vitamin C can be used to stabilize iTregs generated in vitro," says LJI Instructor Xiaojing Yue, Ph.D., who served as co-first author for the EMBO Reports study. "We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation." The recent study, led by LJI Professor Anjana Rao, Ph.D., and Emory Instructor Benjamin G Barwick, Ph.D., builds on the previous discovery that Vitamin C can enhance the enzymatic activity of TET proteins and prompt the generation of stable iTregs under lab conditions. This finding was encouraging, but the scientists did not want to work toward new autoimmune therapies without first analyzing the gene expression patterns and other key epigenetic features of the induced Tregs.  "We wanted to study the entire system at a whole genome level using next generation sequencing technology to better understand the molecular features of these cells," says Yue. Study co-first author Daniela Samaniego-Castruita, a graduate student at LJI, spearheaded the analysis of gene expression and epigenetic changes in the iTregs. A major type of epigenetic modification involves the DNA itself through the addition or removal of molecules called methyl groups from cytosines, one of the four DNA bases. The methyl groups can be further oxidized by TET enzymes. All of these interactions can eventually change how cells "read" the DNA code.  Another type of epigenetic change involves the alteration of DNA accessibility: whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression. In their analysis, the researchers found TET proteins are absolutely required for maintaining the gene expression and epigenetic features that make Tregs as what they are; and adding Vitamin C led to iTregs with similar similar gene expression and epigenetic features as normal "wild type" Tregs found in the body. The study also reveals an intriguing connection between TET enzymatic activity, Vitamin C and IL-2/STAT5 signaling. "In mice that are deficient for components of IL-2/STAT5 signaling, such as IL-2, IL-2 receptors or STAT5, the Tregs cannot develop properly or they can have impaired function," Yue says. The researchers demonstrate that on one hand, TET-deficiency in Treg cells leads to impaired IL-2/STAT5 signaling; on the other hand, Vitamin C confers iTregs enhanced IL-2/STAT5 signaling by increasing the expression level of IL-2 receptor and the functional form of STAT5, and STAT5 binding to essential regions in the genome, rendering these cells survive better in tough environments with low IL-2 supplementation. "We are looking for more small molecules to stabilize TET activity and generate induced Tregs that are even more stable," says Yue. "These induced Tregs could eventually be used to treat patients." "This research gives us a new way to think about treating autoimmune diseases," says Samaniego-Castruita.       Resveratrol ameliorates high-fat-diet-induced abnormalities in liver glucose metabolism in mice via the AMPK pathway Hebei Medical Institute (China), July 19, 2021 A new study on high fat diet is now available. According to news originating from the Department of Internal Medicine by NewsRx correspondents, research stated, “Diabetes mellitus is highly prevalent worldwide.” Our news reporters obtained a quote from the research from Department of Internal Medicine: “High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase b (CaMKKb), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKb inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes.” According to the news editors, the research concluded: “These effects are mediated through the activation of AMPK by PP2A and CaMKKb.”     Hundreds of chemicals, many in consumer products, could increase breast cancer risk List includes potential carcinogens that act by stimulating production of hormones that fuel breast tumors Silent Spring Institute, July 22, 2021 Every day, people are exposed to a variety of synthetic chemicals through the products they use or the food they eat. For many of these chemicals, the health effects are unknown. Now a new study shows that several hundred common chemicals, including pesticides, ingredients in consumer products, food additives, and drinking water contaminants, could increase the risk of breast cancer by causing cells in breast tissue to produce more of the hormones estrogen or progesterone. "The connection between estrogen and progesterone and breast cancer is well established," says co-author Ruthann Rudel, a toxicologist and research director at Silent Spring Institute. "So, we should be extremely cautious about chemicals in products that increase levels of these hormones in the body." For instance, in 2002, when the Women's Health Initiative study found combination hormone replacement therapy to be associated with an increased risk of breast cancer, women stopped taking the drugs and incidence rates went down. "Not surprisingly, one of the most common therapies for treating breast cancer is a class of drugs called aromatase inhibitors that lower levels of estrogen in the body, depriving breast cancer cells of the hormones they need to grow," adds Rudel. To identify these chemical risk factors, Rudel and Silent Spring scientist Bethsaida Cardona combed through data on more than 2000 chemicals generated by the U.S. Environmental Protection Agency (EPA)'s ToxCast program. The goal of ToxCast is to improve the ability of scientists to predict whether a chemical will be harmful or not. The program uses automated chemical screening technologies to expose living cells to chemicals and then examine the different biological changes they cause. Reporting in the journal Environmental Health Perspectives, Rudel and Cardona identified 296 chemicals that were found to increase estradiol (a form of estrogen) or progesterone in cells in the laboratory. Seventy-one chemicals were found to increase levels of both hormones. The chemicals included ingredients in personal care products such as hair dye, chemical flame retardants in building materials and furnishings, and a number of pesticides. The researchers don't yet know how these chemicals are causing cells to produce more hormones. It could be the chemicals are acting as aromatase activators, for instance, which would lead to higher levels of estrogen, says Cardona. "What we do know is that women are exposed to multiple chemicals from multiple sources on a daily basis, and that these exposures add up." The Silent Spring researchers hope this study will be a wakeup call for regulators and manufacturers in how they test chemicals for safety. For instance, current safety tests in animals fail to look at changes in hormone levels in the animal's mammary glands in response to a chemical exposure. And, although high throughput testing in cells has been used to identify chemicals that activate the estrogen receptor, mimicking estrogen, the testing has not been used to identify chemicals that increase estrogen or progesterone synthesis. "This study shows that a number of chemicals currently in use have the ability to manipulate hormones known to adversely affect breast cancer risk," says Dr. Sue Fenton, associate editor for the study and an expert in mammary gland development at the National Institute of Environmental Health Sciences. "Especially concerning is the number of chemicals that alter progesterone, the potential bad actor in hormone replacement therapy. Chemicals that elevate progesterone levels in the breast should be minimized." The researchers outlined a number of recommendations in their study for improving chemical safety testing to help identify potential breast carcinogens before they end up in products, and suggest finding ways to reduce people's exposures, particularly during critical periods of development, such as during puberty or pregnancy when the breast undergoes important changes. The project is part of Silent Spring Institute's Safer Chemicals Program which is developing new cost-effective ways of screening chemicals for their effects on the breast. Knowledge generated by this effort will help government agencies regulate chemicals more effectively and assist companies in developing safer products.     Antioxidant activity of limonene counteracts neurotoxicity triggered by amyloid beta 1-42 oligomers in cortical neurons University of Naples (Italy), July 19, 2021 According to news reporting from Naples, Italy, by NewsRx journalists, research stated, “Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer's disease (AD).” The news editors obtained a quote from the research from School of Medicine: “In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus * * Citrus* * , against the neurotoxicity elicited by Ab [ [1-42] ] oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman's colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of K [ [V] ] 3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC [ [50] ] almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 g/mL, limonene counteracted the increase of ROS production triggered by Ab [ [1-42] ] oligomers, thus preventing the upregulation of K [ [V] ] 3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Ab [ [1-42] ] -induced toxicity.” According to the news editors, the research concluded: “Collectively, the present results showed that the antioxidant properties of the main component of the genus * * Citrus* * , limonene, may be useful to prevent neuronal suffering induced by Ab [ [1-42] ] oligomers preventing the hyperactivity of K [ [V] ] 3.4.”     Meditation And Yoga Change Your DNA To Reverse Effects Of Stress, Study Shows Coventry University (UK), July 22, 2021 Many people participate in practices such as meditation and yoga because they help us relax. At least those are the immediate effects we feel. But much more is happening on a molecular level, reveal researchers out of Coventry University in England. Published in the journal Frontiers in Immunology, this new research examined 18 studies on mind-body interventions (MBIs). These include practices such as mindfulness meditation and yoga. Comprehensively, these studies encompassed 846 participants over 11 years. The new analysis reveals that MBIs result in molecular changes in the human body. Furthermore, researchers claim that these changes are beneficial to our mental and physical health. Body's Response to Stress Causes Damage To elaborate, consider the effect that stress has on the body. When we are under stress, the body increases the production of proteins that cause cell inflammation. This is the natural effect of the body's fight-or-flight response. It is widely believed that inflammation in the body leads to numerous illnesses, including cancer. Moreover, scientists also deduct that a persistent inflammation is more likely to cause psychiatric problems. Unfortunately, many people suffer from persistent stress, therefore they suffer from pro-inflammatory gene expression. But there is good news! According to this new analysis out of Coventry, people that practice MBIs such as meditation and yoga can reverse pro-inflammatory gene expression. This results in a reduced risk of inflammation-related diseases and mental conditions. Lead investigator Ivana Buric from Coventry University's Centre for Psychology, Behaviour and Achievement stated: Millions of people around the world already enjoy the health benefits of mind-body interventions like yoga or meditation, but what they perhaps don't realise is that these benefits begin at a molecular level and can change the way our genetic code goes about its business. These activities are leaving what we call a molecular signature in our cells, which reverses the effect that stress or anxiety would have on the body by changing how our genes are expressed. Put simply, MBIs cause the brain to steer our DNA processes along a path which improves our wellbeing. More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition. But this is an important foundation to build on to help future researchers explore the benefits of increasingly popular mind-body activities.               Large-scale study finds greater sedentary hours increases risk of obstructive sleep apnea Study finds that maintaining an active lifestyle can reduce the risk of OSA, encourages physicians to recommend exercise-based interventions for those at risk Brigham and Women's Hospital, July 22, 2021 A new study by investigators from Brigham and Women's Hospital examined the relationship between active lifestyles and the risk of obstructive sleep apnea (OSA). The study followed around 130,000 men and women in the United States over a follow-up period of 10-to-18 years and found that higher levels of physical activity and lower levels of sedentary behavior were associated with a lower risk of OSA. Their results are published in the European Respiratory Journal.  "In our study, higher levels of physical activity and fewer hours of TV watching, and sitting either at work or away from home were associated with lower OSA incidence after accounting for potential confounders," said Tianyi Huang, MSc, ScD, an Associate Epidemiologist at the Brigham. "Our results suggest that promoting an active lifestyle may have substantial benefits for both prevention and treatment of OSA."  OSA is a type of sleep apnea in which some muscles relax during sleep, causing an airflow blockage. Severe OSA increases the risk of various heart issues, including abnormal heart rhythms and heart failure.  Using the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII) and Health Professionals Follow-Up Study (HPFS), the research team used statistical modeling to compare physical activity and sedentary hours with diagnoses of OSA. Both moderate and vigorous physical activity were examined separately and both were strongly correlated with lower risk of OSA, showing no appreciable differences in the intensity of activity. Moreover, stronger associations were found for women, adults over the age of 65 and those with a BMI greater than or equal to 25 kg/m2.  "Most prior observational studies on the associations of physical activity and sedentary behavior with OSA were cross-sectional, with incomplete exposure assessment and inadequate control for confounding," said Huang. "This is the first prospective study that simultaneously evaluates physical activity and sedentary behavior in relation to OSA risk."  This study also differs from others because of its large sample size and detailed assessment pf physical activity and sedentary behaviors. The research team was able to take many associated factors into account, making the findings more credible.  The authors note that all collected data, both of OSA diagnosis and physical activity or sedentary behavior, were self-reported. While all study participants were health professionals, mild OSA is often difficult to detect and can remain clinically unrecognized. Furthermore, only recreational physical activity was taken into consideration, leaving out any physical activity in occupational settings. Sedentary behavior was only counted as sitting while watching TV and sitting away from home or at work.  According to Huang, the next research steps would be to collect data using actigraphy, home sleep apnea tests and polysomnography, rather than self-reports.  In light of the findings, investigators encourage physicians to highlight the benefits of physical activity to lower OSA risk.  "We found that physical activity and sedentary behavior are independently associated with OSA risk," said Huang. "That is, for people who spend long hours sitting every day, increasing physical activity in their leisure time can equally lower OSA risk. Similarly, for those who are not able to participate in a lot of physical activity due to physical restrictions, reducing sedentary hours by standing or doing some mild activities could also lower OSA risk. However, those who can lower sedentary time and increase physical activity would have the lowest risk."

T cells are a part of your immune system, which has many many important parts of course. T cells are particularly important in autoimmunity because the T CELLS ARE WHAT DO THE DAMAGE!!!In my last episode about Hashimoto's I talked about antibody levels and described how will antibodies "flag" something as bad so that immune cells can come destroy it, but antibodies have no destructive properties. The progression and destruction of autoimmune disease is determined by the level of T cell activity! T cells destroy the gut in autoimmunity. T cells destroy the joints in autoimmunity. T cells destroy the thyroid. T cells destroy the myelin of your nerves. THEY ARE IMPORTANT!!What type(s) are there? What do they do? How do I know if mine are working properly?This episode goes through all of that information! I go through the 4 most important polarizations of T cells: Th1 (fights intracellular infections)Th2 (produces mucus and expels allergens and parasites)Th17 (causes tissue-damaging inflammation)Regulatory T cells (Tregs), which are the peacemakers that dampen inflammationAutoimmunity ALWAYS has an imbalance of too much Th17 activity and not enough Treg activity, but what about Th1/Th2? Eventually MOST autoimmune patients will present with decreased Th1 and increased Th2, and in this episode I go through some of the details of how this happens, how the patient presents and how this needs to be handled clinically to get it under control!

Listen to Dr. Azza Gadir explain to Heather the functions of the immune system and the difference between getting the COVID-19 vaccine vs. natural infection or avoiding the virus. Dr. Gadir teaches us about allergies, autoimmune conditions, the microbiome, and the science behind vaccination. She also addresses how women’s health, menstrual cycles, pregnancy and fertility are impacted by the various coronavirus vaccines. Dr. Gadir addresses common pandemic concerns with transparency and research. In this episode, Heather and Azza discuss: How the immune system helps us maintain homeostasis and protects us from disease The importance of herd immunity How the vaccine affects fertility, pregnancy and menstrual cycles Why so many people feel uncertain about whether the vaccine is right for them, and how they made their own vaccination decisions How vaccines don't necessarily change the immune system, but rather give the immune system something to respond to Allergies vs intolerances Autoimmune conditions Impact of genetics, environment and diet on immunity Innate immune system and the adaptive immune system The gut microbiome Regulatory T-cells, antibodies, antigen presenting cells, spike proteins, dendritic cells Antigen specificity Vaccines as a form of training the body The memory of our bodies COVID-19 vaccination and women’s periods and fertility Different types of vaccines, including the mRNA vaccines Who should be careful about getting vaccinated The importance of supporting frontline healthcare workers who have experienced a lot of trauma in the pandemic Ingredients of the Moderna (p. 11) and Pfizer (p. 11) COVID19 vaccines (overview) Dr. Azza Gadir completed her PhD in Immunology from University College London and spent the next 7 years at Harvard Medical School / Boston Children’s Hospital where her published research focused on understanding the immune system and how it protects us from diseases like allergies. Recently she has worked for biotech companies exploring how academic research can be used to create innovative therapeutic products. Dr. Gadir grew up in London and received a Masters degree in the Immunology of Infectious Diseases from the London School of Hygiene and Tropical Medicine. Dr. Azza Gadir on LinkedIn. Heather Grzych is the author of The Ayurvedic Guide to Fertility and the host of the Wisdom of the Body podcast. A board-certified Ayurvedic practitioner, she bridges the worlds of conventional and alternative medicine to help women and men heal their physical and emotional lives. Heather is on the board of directors for the National Ayurvedic Medical Association (NAMA) and has consulted with doctors, governments, and insurance companies. She offers virtual consultations and programs worldwide. www.heathergrzych.com   Connect with Heather: Instagram.com/heathergrzych Facebook.com/grzychheather   This podcast is for educational and entertainment purposes only.

Regulatory T cell therapies have been pursued as treatment for cancers, but Sonoma Biotherapeutics believes these cells can be harnessed to delivery lasting and potential curative treatments for autoimmune and degenerative diseases. We spoke to Jeff Bluestone, CEO of Sonoma, about regulatory T cell therapies, why they may have broad application in a range of conditions, and what challenges will need to be overcome to usher in an area of cell therapies beyond cancer.

Regulatory T cells are an incredibly important part of a healthy immune system. Many of the chronic diseases that we face including, autoimmune diseases, require modification of the immune system in order to support healing. In today's episode we discuss various pharmacological and natural methods that have been shown to regulate Tregs production and function. Research DiscussedMedical treatment can unintentionally alter the Treg compartment in patients with widespread pathophysiologic conditions https://ajp.amjpathol.org/article/S0002-9440(20)30369-2/fulltextThe role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic reviewhttps://pubmed.ncbi.nlm.nih.gov/31550254/Metformin reduces autoimmune antibody levels in patients with Hashimoto's thyroiditis: A systematic review and meta-analysishttps://pubmed.ncbi.nlm.nih.gov/32741222/Promotion of regulatory T cell induction by immunomodulatory herbal medicine licorice and its two constituentshttps://www.nature.com/articles/srep14046Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthmahttps://pubmed.ncbi.nlm.nih.gov/20889543/Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factorshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738975/N‐acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double‐blind, placebo‐controlled trial†https://onlinelibrary.wiley.com/doi/full/10.1002/art.34502Immune Responses Regulated by Cannabidiolhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173676/Influence of Dietary Components on Regulatory T Cellshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276397/Stay in touch!Naturopathic Clinical Mentorship https://www.naturopathicmentorship.com/Next AWT Program launches September 14th - register now or book a call for more information! https://www.naturopathicmentorship.com/program-applicationAdvanced Women's Health website https://www.advancedwomenshealth.ca/My personal website and articles https://sarahwilsonnd.com/Finally Lose It purchase https://sarahwilsonnd.com/finallyloseitInstagram https://www.instagram.com/drsarah_nd/ Facebook https://facebook.com/sarahwilsonndLive in Ontario? Book an appointment! https://www.advancedwomenshealth.ca/book-nowOne on One professional consult 

Dr. Peter Attia Peter is the founder of Attia Medical, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity and optimal performance. In addition to being a medical doctor, Dr. Attia has done research on the role of regulatory T cells in cancer regression and other immune-based therapies for cancer. Regulatory T cells have also been, in the past, referred to as suppressor T cells because of their role in actually attenuating or reducing the inflammatory response. Dr. Attia and I share interests in all things related to longevity and healthspan, which includes the role of diet, nutrition, sleep, exercise, and stress. Dr. Attia is a medical doctor and specializes in implementing these strategies in clinical practice. You can learn more about that at his website www.attiamedical.com.   If you're interested in learning more, you can read the full show notes here: https://www.foundmyfitness.com/episodes/peter-attia Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

[intro music]   Hello, and welcome to Episode Thirty-One of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Lloyd Kasper about the gut microbiome and its role in MS. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Last week our parent organization, the Accelerated Cure Project, launched its latest endeavor called “iConquerMS.” iConquerMS aims to enroll 20,000 people living with MS to play an active role in research, empowering them to securely submit their health data, influence the studies that are carried out by the initiative, and stay informed about the research. Visit iConquerMS.org for more information.   Vision and sensorimotor problems go together in some MS patients. A recent publication in the journal Neurology examined the relationship between MRI measures of the spinal cord and retina in patients with MS. The investigators found some correlation between the two types of metrics, but they also found that damage in each structure had independent relationships with disability. Read the full story in our “news and future directions” section.   And lastly, our previous podcast contained an error. We mentioned a story about a proof-of-concept study of a novel way to monitor lesion repair. However, the story was withheld from publication due to a delay in the release of the research article. The story is now live on our website.   [transition music]   Now to the interview. Dr. Lloyd Kasper is a faculty member of the Geisel School of Medicine at Dartmouth College. He met with MSDF Executive Editor, Bob Finn, to talk about his research on the gut microbiome and MS.   Interviewer – Robert Finn Dr. Kasper, welcome.   Interviewee – Lloyd Kasper Thank you.   MSDF So to start, why on earth would someone interested in a neurological disease such as MS concern himself with bacteria in the intestines; what’s the connection?   Dr. Kasper That’s actually a very valid question. And the answer to that question is pretty straightforward, is that there’s a very clear brain-gut access so that the brain talks to the gut primary modulating the physiology of the gut through secretion of a variety of molecules, vasoactive proteins, etc. That in turn affects the motility of the gut. By affecting the motility of the gut, you also affect everything that’s inside the gut, which is – as you mentioned just previously – the 100 trillion bacteria that each and every one of us in this world has. And those bacteria in response to the changes in motility shift their behavior, because these are living organisms, and they secrete a wide range of metabolites.   For the purposes of simplicity, you can look at those metabolites and the effect of those various metabolites on the immune system, taking into account that the gut is the largest immune system in our body – 80% of our immune cells are in the gut. So you’ll have this clear interaction between the brain, its activity physiologically on the gut, and the gut’s activity on the bacteria, and then the bacteria’s activity back on the immune system which leads to issues related to the brain.   MSDF So you partly answered my next question. There are microbiomes in other places besides the gut – the skin, the urinogenital tract, etc. Do those other microbiomes have any affect or any relationship to multiple sclerosis, do you think?   Dr. Kasper First of all, the association between the gut microbiome and MS has not yet been fully established, there’s experimental data that would suggest that there is a relationship between the two but that’s still at the experimental level. There really has been very little exploration of the other microbiomes within the body. Remember, the microbiome is not just the microflora. What the microbiome is is the genome of the flora in its relationship to the genome of its host. So when you look at the genomics of MS, for example, in the host – which there’s a lot of work that’s being done – you’re only looking at a fraction of the genetic material that’s involved in this relationship between the gut and the body that it’s in OR any of the other sites that we have microflora – our mouth, as you pointed out; our ears – inside of our ears; our lungs. Those are all areas that bacteria in our body exists in balance with us to achieve a homeostasis. The reason for looking at the gut microbiome is that because it’s the largest, probably the most complex as well.   MSDF So you focused much of your attention on a single bacterial species. Let me see if I pronounce this correctly – Bacteroides fragilis– am I close?   Dr. Kasper Correct.   MSDF And a single substance that it produces, polysaccharide A, or PSA – which has no relation to prostate specific antigen. Why are you focusing on that species and that product?   Dr. Kasper Well, there is mounting evidence that there are several phyla that colonize the gut. The two major phyla of interest are Firmicutes, which are gram-positive aerobes, and Bacteroides, which are gram-negative anaerobes. I’m talking about at the phyla level over which there is no kingdom, phylum, class, order, family, genus, species. Under each one of those phyla there are many different species. We’ve focused in on primarily Bacteroides because Bacteroides fragilis is a very common commensal that essentially inhabits in the neighborhood of 80-90% of all mankind in the world. Bacteroides as a phyla has been associated with the induction of regulatory T cells. Regulatory T cells live in the colon, in and around the colon, and that’s where Bacteroides live. And it’s been shown that Bacteroides as a phyla have the capacity to drive regulatory T cells.   The reason it’s important in MS is because there is a known deficit in the regulatory T cell population in patients with MS. And we chose Bacteroides fragilis because of all the Bacteroides species, that’s the one that we actually know most about immunologically. There’s at least 20 or 25 years’ worth of very, very important data that shows how this particular molecule, this polysaccharide A – and it’s a polysaccharide, it’s not a peptide, it’s a polysaccharide – how this polysaccharide can drive the immune system to a regulatory phenotype that’s associated with the induction of regulatory T cells, production of IL10, all those factors which are important in MS which we know are deficient in those with MS.   MSDF When you say drive the immune system, drive T regs, what do you mean by that?   Dr. Kasper Basically, these bacteria have the capacity to convert effector cells, which would be CD4 positive CD25 negative cells to a regulatory phenotype, which would be CD4 CD25 positive associated with sort of the standard-bearer of regulatory cells, which is Foxp3, which is a nuclear antigen that’s been characterized with it. So this molecule has a remarkable capacity to do that both in vivo and our studies show you can do that actually in vitro as well. So you can take cells that are negative that would be considered naïve or effector-type cells, culture them with this PSA molecule, and convert them to regulatory cells which we know are important in controlling the disease.   MSDF So remind me whether you want more or fewer of these regulatory T cells.   Dr. Kasper It depends where you are in life. To give you sort of a circumstantial argument, we know that Firmicutes, which is that other major phyla, has been associated with a number of disease states, including obesity – just to name one – atherosclerosis, but we also know that the Firmicutes have the capacity to drive IL-17. The regulatory T cells are cells that control the IL-17 response, so it’s important to have regulatory T cells to control the IL-17. We know experimentally that IL-17 drives the experimental form of multiple sclerosis EAE, and there is mounting data – and pretty conclusive, I think – MS is probably at least in part driven by IL-17 cells. So you need these regulatory T cells to control that IL-17 response which is probably being driven by the Firmicutes population. And I’m oversimplifying this, because you remember, you’ve got a hundred trillion cells downstairs making god knows how many different metabolites with over a million genes. So what I’m presenting to you is a very simplified version of this remarkably complex organ.   MSDF So is this leading toward clinical utility for polysaccharide A?   Dr. Kasper We hope so.   MSDF Can you tell me more about that?   Dr. Kasper Well, again, our experimental data – at least in EAE – demonstrates that animals that have been induced with EAE are protected by this polysaccharide. Animals that have EAE, we can therapeutically treat them with this. So this is the first demonstration that a commensal-derived bacterial product that’s within essentially pretty much all of mankind has the capacity to induce regulatory T cells. We don’t know if MS patients are deficient in this or they have the genetic makeup that they can’t respond to it, or whatever it may be. As I said, there’s a real complexity. But the simple observation as we know is that if we take animals that are susceptible to EAE and we treat the prophylactically or therapeutically, we’re able to protect them very, very nicely against the disease process.   And now we have preliminary data in humans that we can take human cells in vitro out of a person and we can drive those human cells from an effector CD4-positive CD25-negative phenotype to a regulatory phenotype by this molecule; just five days of exposure and you see this very nice conversion that’s associated with increased IL10 protection, etc.   MSDF Do you imagine that the PSA molecule itself, if drug development goes on, is there any chemistry that needs to be done before it might possibly be therapeutic?   Dr. Kasper A lot of the chemistry has been done. We have a pretty good idea of what the molecule looks like, it’s a repeating polysaccharide chain. And we know what the conditions are at least in animals as far as innate response molecules – TLRs, toll-like receptors, etc. So as far as the molecule itself, I think we have a pretty good understanding. As I said, there’s about 20 years’ worth of very solid biology behind this molecule. So how far we are away from the clinic at this point is a matter of time, resources, and money to be able to move it from the experimental stage that we’re in into the clinic.   MSDF So you’re not the only research group working on the connection between the gut microbiome and multiple sclerosis. I wonder if you can talk a little bit about how your research fits in with the various other approaches that are going on.   Dr. Kasper Our research has been focused primarily on immune regulation – how to get the disease under control, at least experimentally and hopefully in MS patients. Most of the other labs are looking primarily at what bacteria or bacteria populations are responsible for affecting the disease; what’s driving the disease. We’ve sort of kept away from that because we were fortunate in being able to find this one molecule derived from a bacteria, as I said, that much of mankind is colonized with, so we’ve been focused mostly on how to regulate the disease rather than what’s driving the disease.   MSDF Now, as you know, there’s been a lot of talk and controversy about the role of diet in multiple sclerosis. Do you think that gut bacteria and the substances they product may provide that missing link connecting diet with MS.   Dr. Kasper I think that diet’s going to turn out to be one of the more critical environmental factors that’s associated with the disease process.   MSDF Can you say a little bit more about that?   Dr. Kasper Well, if you look at all the risk factors that we know for MS, that being genetics, obesity, smoking, gender – just to name a few – there’s about six or seven of them. Every one of those risk factors is associated with the microbiome. The common denominator for all the risk factors we know so far in MS is the microbiome, and that includes genetics. As I said, the microbiome is a two-way street; it induces things in us and we do things in turn to it, so it’s a binary system. So our speculations – and we just had a paper published in FEBs – Federation of Experimental Biology – is we’re speculating that the gut microbiome is the major environmental risk factor for MS because it includes all of the known risk factors.   So how can you adjust that? Well, the most logical way is diet, right, because it’s the change in the human diet over the last hundred years that may be accountable for the rise in the disease process. It may also be the change in the diet in Africa as well as Asia which were relatively unknown for MS, but now the incidents in Asia as well as in Africa is approaching about the same as it is in the United States and Europe. So as diet has changed, so has the incidence of the disease gone up. So I’m speculating that diet will turn out to be a very important factor in controlling the microflora, which in turn allows for the balance, the homeostasis, in individuals.   MSDF Well, very interesting. We’ve come to the end of our time, but is there anything you’d like to add, any important questions that I haven’t asked that I should have asked?   Dr. Kasper No. I think the question about the diet, you know, where do you go from here? Because it’s going to take years and years for scientists and clinicians to sort out what’s actually going on in the microbiome. We’re at the tip of the iceberg in this really, because not only is it the immunology that’s important but it’s the physiology and the physiologic changes that the gut microbiome may be creating in people. So as we get better definition of what activities are going on in the microbiome, the greater the likelihood we’ll have of understanding a whole range of human diseases. And not just MS, but that’s all other autoimmune diseases, cancer, obesity, you know, it’s a long list.   And it may ultimately turn out that it’s a clue to our understanding of cancer, for example, because as the microflora shifts as we grow older – which it does – perhaps what we’re seeing is that early on we have bacteria that induce inflammatory processes – which is why MS is a disease of young people – that tends to peter out as you get older. It’s a well-known thing. It doesn’t go away but it tends to peter out. But that may be parallel to the shift in the microflora that’s going on. So early on in the western diet you’re having mostly Firmicutes. As we get older that shifts to more of Bacteroides, which has more regulation. What does more regulation equal? Well, you’re down-regulating the immune system, and as we get older what do we become susceptible? Cancer. So there’s a real balance that’s going on here. And I think a lot of the clues to human biology as far as disease state are going to ultimately be related to the microbiome.   MSDF Dr. Kasper, thank you very much.   Dr. Kasper Thank you.   [transition music]   Thank you for listening to Episode Thirty-One of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]  

Summary: Allergic diseases have exponentially increased during the last decades. The complexity of its aetiology is due to multifaceted interactions between genetic and environmental factors on the development of the immune system. While advances of technology have identified allergy susceptibility genes, functional assays are needed to better understand the underlying mechanisms. Epidemiological studies have consistently shown that rural/farm environments are protective for the development of allergic diseases, including asthma and atopic sensitization. Importantly, prenatal and early life exposures have been shown to confer the strongest protection effects. The mechanisms of how farming modulates the immune system are still not disentangled in detail but include regulation of innate receptors and Regulatory T cells. In the herewith presented thesis, the following main findings were achieved in the context of genetic and immunological influences on development of allergic disease in two different birth cohort studies: First, 200 neonates were assessed for genetic influence of polymorphisms on neonatal immune responses and development of allergic diseases in childhood. The present study suggested a role for polymorphisms in the Th2-pathway, particularly for STAT6 rs324011, on immune regulation at an early stage of immune maturation, namely significantly lower Treg-associated gene expression and Th1-polarization. Polymorphisms in the Th1-pathway, namely the transcription factors TBX21 and HLX1, were shown to be relevant in shaping early immune responses and mainly Th2 cytokines at birth. Th1 and Th2 genotype-related immune responses at birth were partially associated with development of allergic diseases and/or protection during early life. These children are currently followed until the age of 6 years to further investigate allergic and respiratory disease during age-related immune maturation. Secondly, almost 150 children were investigated at the age of 6 years to assess the role of regulatory T cells in relation to farm exposures and clinical outcomes of allergic diseases. Our data indicated an inverse association of farm exposures and the prevalence of asthma during childhood. Children exposed to hay, stable and farm milk had a lower prevalence of asthma. Regarding underlying immune mechanisms, we have detected that children with contact to hay have increased levels of Treg cells and that farm milk intake earlier during childhood can still be partially reflected on Treg cells levels at age 6 years. Assessing Treg functional mechanisms, changes in cytokine secretion were observed depending on the farming and asthmatic status of the children, however confirmation in a larger number of children is required In summary the present work indicated that Th1 and Th2 polymorphisms were associated with modulated immune responses already at birth and influenced allergic disease development during the first three years of life. Furthermore, farm exposures were associated with a lower prevalence of asthma and associated with modulation of regulatory T cell frequency in German children at age 6 years.

Regulatory T-cells (Treg) are important regulators of immune responses. In AML patients before/after immunotherapy (stem-cell-transplantation (SZT) or donor-lymphocyte-infusion (DLI)) their suppressive role can contribute to suppress severe graft-versus-host-reactions (GVHD), but also to impair antileukemic reactions. Aim: Since leukemia-derived dendritic-cells (DCleu) are known to improve antileukemic functionality of T-cells we evaluated the composition and development of distinct Treg-subtypes in AML-pts (n=12) compared to healthy probands (n=5) under unstimulated conditions and during stimulation with DCleu-containing DC (‘DC’) or blast-containing mononuclear cells (‘MNC’) in 0-7 days mixed lymphocyte cultures (MLC) by flowcytometry. T-cell-subgroups in AML pts were correlated with antileukemic functionality before and after ‘DC’ or ’MNC’ stimulation by functional fluorolysis-assays. Results: 1. AML-pts’ T-cells presented with significantly higher frequencies of Treg-subgroups in unstimulated T-cells compared to healthy probands. 2. After 7 days of ‘DC’ or ‘MNC’-stimulation all Treg-subtypes generally increased; significantly higher frequencies of Treg-subtypes were still found in AML-pts. 3. Antileukemic cytotoxicity was achieved in 36% of T-cells after ‘MNC’- compared to 64% after ‘DC’-stimulation. Antileukemic activity after ‘DC’ but not after ‘MNC’-stimulation correlated with significantly lower frequencies of Treg-subtypes (CD8+ Treg/Teff/em reg). Furthermore, cut-off-values for Treg subpopulations could be defined allowing a prediction of antileukemic response. Conclusion: We demonstrate a crucial role of special Treg-subtypes in the mediation of antileukemic functionality. High CD8+Treg, Teff/em reg and CD39+T-Zellen clearly correlated with reduced antileukemic activity of T-cells. ‘DC’ stimulation of T-cells contributes to overcome impaired antileukemic T-cell-reactivity. Refined analyses in the context of clinical responses to immunotherapy and GVHD reactions are required.

Regulatory T cells (T-reg) are important regulators of immune responses. In acute myeloid leukemia (AML) patients before/after immunotherapy (stem cell transplantation or donor lymphocyte infusion), their suppressive role can contribute to suppress severe graft-versus-host reactions, but also to impair antileukemic reactions. As leukemia-derived dendritic cells (DCleu) are known to improve the antileukemic functionality of T cells, we evaluated the composition and development of distinct T-reg subtypes in AML patients (n = 12) compared with healthy probands (n = 5) under unstimulated conditions and during stimulation with DCleu-containing DC (DC) or blast-containing mononuclear cells (MNC) in 0- to 7-day mixed lymphocyte cultures by flow cytometry. T-cell subgroups in AML patients were correlated with antileukemic functionality before and after DC or MNC stimulation by functional fluorolysis assays. (1) AML patients' T cells presented with significantly higher frequencies of T-reg subgroups in unstimulated T cells compared with healthy probands. (2) After 7 days of DC or MNC stimulation, all T-reg subtypes generally increased; significantly higher frequencies of Treg subtypes were still found in AML patients. (3) Antileukemic cytotoxicity was achieved in 36% of T cells after MNC compared with 64% after DC stimulation. Antileukemic activity after DC but not after MNC stimulation correlated with significantly lower frequencies of T-reg subtypes (CD8(+) T-reg/T-eff/em reg). Furthermore, cut-off values for T-reg subpopulations could be defined, allowing a prediction of antileukemic response. We demonstrate a crucial role of special T-reg subtypes in the mediation of antileukemic functionality. High CD8(+) T-reg, T-eff/em reg, and CD39(+) T cells correlated clearly with a reduced antileukemic activity of T cells. DC stimulation of T cells contributes to overcome impaired antileukemic T-cell reactivity. Refined analyses in the context of clinical responses to immunotherapies and graft versus host reactions are required.

Regulatory T-cells (Tregs), characterized as CD4+CD25(hi) T-cells expressing FOXP3, play a crucial role in controlling healthy immune development during early immune maturation. Recently, FOXP3 demethylation was suggested to be a novel marker for natural Tregs in adults. In cord blood, the role and function of Tregs and its demethylation is poorly understood. We assessed FOXP3 demethylation in cord blood in relation to previously used Treg markers such as CD4+CD25(hi), FOXP3 mRNA, protein expression, and suppressive Treg function.