Scientists map surface of immune cells

June 12, 2015 (Helmholtz Zentrum München) The team headed by Dr. Kathrin Suttner, who, together with Prof. Dr. Carsten Schmidt-Weber, heads the airway immunology research group at the Helmholtz Zentrum München and Technische Universität München, concentrated its work on the so-called naive CD4+ T cells. They are a precursor form of T cells and form the basis for immunological memory. Impaired development of these cells can influence the entire immune system and lead to illnesses such as allergies and asthma. Protein atlas on T cell precursors The scientists specifically examined proteins on the surface of the naive CD4+ T cells because these proteins play an important role in the cell development and mediate the corresponding responses to stimuli from the environment. Using mass spectrometry and bioinformatic analysis in close cooperation with the Core Facility Proteomics of the Helmholtz Zentrum München and the Bioinformatics and Computational Biology Department of the Technische Universität München, the researchers succeeded in precisely identifying a multitude of surface proteins ("A combined omics approach to generate the surface atlas of human naive CD4+ T cells during early TCR activation"). They also compared the compositions in the early and late activation forms of the cells. "We can understand the results as an atlas for surface proteins. The findings also presented proteins for the first time that had never been known to be associated with T cells or their maturation process," explains Anke Grässel, first author of the study. The researchers are planning further investigations in the future in order to explain the exact role of these proteins. "We want to contribute to identifying new targets of attack that could serve as a basis for the development of therapeutic or diagnostic approaches," explains group [...]

Discovery could help reverse glucocorticoid resistance in some young leukemia patients

St. Jude Children’s Research Hospital study lays the foundation for more effective treatment of childhood leukemia and a wide range of other disorders using small molecules to reverse glucocorticoid resistance Memphis, Tennessee, May 4, 2015 Researchers led by St. Jude Children’s Research Hospital scientists have identified a mechanism that helps leukemia cells resist glucocorticoids, a finding that lays the foundation for more effective treatment of cancer and possibly a host of autoimmune diseases. The findings appear online today in the scientific journal Nature Genetics. The research focused on glucocorticoids, a class of steroid hormones. These hormones have been key ingredients in the chemotherapy cocktail that has helped to push long-term survival for the most common childhood cancer to 85 percent nationwide and about 94 percent at St. Jude. Young acute lymphoblastic leukemia (ALL) patients whose cancer is resistant to steroids are less likely to survive. Yet the cause of resistance is often unknown. In this study, scientists identified a mechanism responsible for about one-third of steroid resistance in children and adolescents with ALL. Additional research is needed to determine if the process is at work in adults with ALL, where steroid resistance is more common and long-term survival lags. “Based on these findings, research has already begun to identify small molecules with the potential to reverse glucocorticoid resistance, leading to more effective treatment and increased survival,” said the paper’s corresponding author, William Evans, Pharm.D., a member of the St. Jude Department of Pharmaceutical Sciences. “Glucocorticoids are widely used to treat asthma, rheumatoid arthritis, colitis and other autoimmune disorders. That means these results have the potential to benefit a wide range of patients.” The study included bone marrow cells from 444 newly identified ALL patients being [...]

Newly Enlisted T-Cell ‘Policemen’ Can Slow Down Run-Away Immune System, SLU Scientist Says

March 30, 2015 Carrie Bebermeyer, Medical Center Communications, Saint Louis University ST. LOUIS — In research published in the March issue of Immunity, Saint Louis University scientists led by Daniel Hawiger, M.D., Ph.D., assistant professor of molecular microbiology and immunology, have discovered that potentially aggressive T-cells that might lead to auto-immune disease can instead be enlisted to help “police” over-active immune responses, via the molecule CD5. The immune system maintains health by avoiding the dangers of over- and under-responses.  People with immune systems that do not efficiently fight off pathogens, like viruses or bacteria, will become sick. On the other hand, an immune system that is too robust may develop autoimmune diseases. Hawiger and colleagues from his laboratory report a breakthrough in understanding the way regulatory T cells, which police other T cells’ responses, develop. The first author of this study is Jacob Henderson, Hawiger’s graduate student. Other researchers on the study include Adeleye Opejin, Andrew Jones and Cindy Gross from Hawiger’s laboratory. T-cells, the immune system’s fighters, are trained to distinguish between self and non-self, with most learning tolerance for self. During the T-cell education process, however, a group of T-cells always develops that remain self-reactive and might turn their attacks on the body’s own cells. These self-reactive T-cells are responsible for the sort of friendly fire that leads to autoimmune diseases like multiple sclerosis. “There is a need to keep those T-cells in check, because otherwise we would have a runaway immune system,” Hawiger said. Hawiger and his group report a mechanism for how potentially self-reactive T-cells can instead be enlisted to become regulatory T cells that police other T cells’ responses. Most of the time, the immune system keeps self-reactive T-cells at bay by [...]

‘Most Comprehensive Map’ of Human Epigenomes Is Unveiled

UCSF Researcher Leads One of Four Major U.S. Centers in Global Effort By Laura Kurtzman on February 18, 2015 Two dozen scientific papers published online simultaneously on Feb. 18, 2015 present the first comprehensive maps and analyses of the epigenomes of a wide array of human cell and tissue types. Epigenomes are patterns of chemical annotations to the genome that determine whether, how, and when genes are activated. Because epigenomes orchestrate normal development of the body, and disruptions in epigenetic control are known to be involved in a wide range of disorders from cancer to autism to heart disease, the massive trove of data is expected to yield many new insights into human biology in both health and disease. The 24 papers describing human epigenomes will appear in print on Feb. 19, 2015 in the journal Nature and in six other journals under the aegis of Nature Publishing Group. Collectively, the papers are a culmination of years of research by hundreds of participants in the Roadmap Epigenomics Program (REP), first proposed in 2006 by academic scientists and key members of the National Institutes of Health. All will be freely available atNature’s Epigenome Roadmap website. “The DNA sequence of the human genome is identical in all cells of the body, but cell types—such as heart, brain or skin cells—have unique characteristics and are uniquely susceptible to various diseases,” said UC San Francisco’s Joseph F. Costello, PhD, director of one of four NIH Roadmap Epigenome Mapping Centers (REMC) that contributed data to the REP. “By guiding how genes are expressed, epigenomes allow cells carrying the same DNA to differentiate into the more than 200 types found in the human body.” In cancer research, said Costello, the new [...]

Breakthrough Research at UH May Lead to Novel Natural-Derived Lupus Treatment

Bio News Texas, by Leonore Mateus Ferrara ~ September 23, 2014 A new treatment for lupus may have been discovered by a group of biomedical engineers from the University of Houston (UH) in Texas, who have developed a drug that, unlike the current treatments for the disease, does not have a long list of side effects and risks. Lupus, or systemic lupus erythematosus, is a progressive and degenerative disease of the immune system that affects a patient’s healthy tissue, cells, and organs. There is no cure for lupus, and one is not expected for the foreseeable future. However, the UH research team led by Chandra Mohan is working on a natural therapy using a plant-derived chemical. During their research, the engineers worked on the use of a synthetic, plant-derived compound, called CDDO, which can be effective in suppressing the development of the disease in murine models, like kidney disease, one of the most common consequences of lupus. One of the medical complications associated with lupus is lupus nephritis, a disease that attacks the kidneys and affects about 40 percent of the lupus patient population. It causes inflammation of the kidneys and disables the organ so that it cannot properly expel body waste and toxins as it normally does. Lupus nephritis not only leads to tens of thousands of hospitalizations yearly, but it can also be deadly. “The development of lupus is a two-step reaction,” said Mohan, as she explained that researchers still do not understand how CDDO is able to suppress lupus progression. ”First, the immune system develops antibodies that attack the body’s own DNA, then that activated immune system attacks the kidneys. We found that CDDO may block both of these steps.” The only [...]

$4.9 million grant to fund AIDS research

Washington University in St. Louis, by Michael C. Purdy ~ January 16, 2014 The AIDS Clinical Trials Site at Washington University School of Medicine in St. Louis has been awarded a National Institutes of Health (NIH) grant that supports testing of treatments for HIV, AIDS and the many complications they cause. The grant, from the National Institute of Allergy and Infectious Diseases, will provide up to $4.9 million over the next seven years to the Washington University site and the researchers’ collaborators at Vanderbilt University. The funding allows the Clinical Trials Site group to continue to recruit patients for testing new ways to treat AIDS and HIV through a nationwide network of research sites known as the AIDS Clinical Trials Group. Centers that belong to the group work cooperatively to enroll patients in trials, making it possible to conduct studies that otherwise might not recruit enough participants. “Our site has been active in the AIDS Clinical Trials Group since 1988, and together we have led the way in optimizing treatments for AIDS,” said principal investigator David Clifford, MD, the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology. “Our work has helped change the prognosis from almost-certain death within a couple years of AIDS diagnosis to life expectancies that are now approaching normal duration.” Among its many accomplishments, the national AIDS Clinical Trials Group has helped develop and test many of the therapies now used to treat AIDS. The group also has made significant contributions to treatment of infections associated with AIDS, including tuberculosis, herpes virus and hepatitis. The group’s research includes efforts to develop a cure for HIV and investigations of the long-term side effects of HIV infection and the drugs used to [...]

FDA Approves MSC-NP Therapy as Investigational New Drug in MS Clinical Trial: A Research Milestone

Research Center of New York, by Staff ~ August 16, 2013 The stem cell research division of the Tisch MS Research Center of New York proudly announces Food and Drug Administration (FDA) approval of autologous, mesenchymal stem cell-derived neural progenitor cells (MSC-NPs) as an Investigational New Drug (IND) for an open label, phase I clinical trial in the treatment of multiple sclerosis. Approximately 20 progressive MS patients, recruited from the existing patient population of the International Multiple Sclerosis Management Practice (IMSMP), will be initially enrolled. The Tisch MS Research Center stem cell trial is the first of its kind in the United States, and incorporates the following key advantages: • MSC-NPs derived from adult autologous mesenchymal stem cells are the primary therapeutic agent. • MSC-NPs display a greater potential for differentiation into mature neural tissue, with lower risk for ectopic differentiation. • MSC-NPs have the capacity for recruitment of existing stem cells within the brain and spinal cord via the induction of immunomodulatory and trophic growth factors. • MSC-NPs will be administered in multiple rounds of treatment rather than a single treatment. • Route of administration will be intrathecal (into the cerebrospinal fluid) in order to directly target regenerative mechanisms in the central nervous system. This FDA approval is the culmination of more than a decade of research into the therapeutic potential of stem cells for MS patients and confirmation of the pioneering approach adopted by the Tisch MS stem cell research team led by Saud Sadiq, MD and Violaine Harris, PhD. The proof-of-concept of this approach was demonstrated in the EAE animal model of MS (Harris et al., J Neurol Sci, 2012). This study showed compelling evidence of the therapeutic potential of intrathecal MSC-NPs [...]

Non-Toxic Therapy For Lupus Successfully Tested On Patients

Red Orbit, by Rebekah Eliason ~ November 12, 2013 Scientists from Northwestern Medicine have brought new hope to patients with lupus. A new nontoxic therapy that suppresses lupus in blood samples was designed and successfully tested on patients with the autoimmune disease. There is hope this treatment will replace the use of toxic drugs that carry nasty side effects with a vaccine like therapy. This new treatment could keep lupus in remission in the body. Lupus is a debilitating autoimmune disease where the body creates auto-antibodies that attack its own healthy tissue. This causes severe pain, inflammation and destruction to many vital organs in the body. The Lupus Foundation of America has estimated that some form of the disease affects 5 million people throughout the world. Previous studies at Northwestern have showed that a nontoxic therapy using small pieces of proteins known as peptides can block lupus in mice prone to contracting the disease. The peptides produce special regulatory T cells that are vital to suppressing the disease. This new study was comprised of 30 lupus patients, ten of whom were active and twenty who were in remission, along with fifteen healthy patients. Each person had a blood sample cultured with low doses of the peptide. Senior study author Syamal Datta, professor of medicine-rheumatology and microbiology-immunology at Northwestern University Feinberg School of Medicine, said, “We found that the peptides could not only generate regulatory T cells, but also that they block and reduce autoantibody production to almost baseline levels in the blood cultures from people with active Lupus.” “This approach shows that the peptides have the potential to work like a vaccine in the human body, to boost the regulatory immune system of those with [...]

MS research could help repair damage affecting nerves

Medical XPress, by Staff ~ July 21, 2013 Multiple sclerosis treatments that repair damage to the brain could be developed thanks to new research. A study has shed light on how cells are able to regenerate protective sheaths around nerve fibres in the brain. These sheaths, made up of a substance called myelin, are critical for the quick transmission of nerve signals, enabling vision, sensation and movement, but break down in patients with multiple sclerosis (MS). The study, by the Universities of Edinburgh and Cambridge, found that immune cells, known as macrophages, help trigger the regeneration of myelin. Researchers found that following loss of or damage to myelin, macrophages can release a compound called activin-A, which activates production of more myelin. Dr Veronique Miron, of the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said: "In multiple sclerosis patients, the protective layer surrounding nerve fibres is stripped away and the nerves are exposed and damaged. "Approved therapies for multiple sclerosis work by reducing the initial myelin injury – they do not promote myelin regeneration. This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis." The study, which looked at myelin regeneration in human tissue samples and in mice, is published in Nature Neuroscience and was funded by the MS Society, the Wellcome Trust and the Multiple Sclerosis Society of Canada. Scientists now plan to start further research to look at how activin-A works and whether its effects can be enhanced. Dr Susan Kohlhaas, Head of Biomedical Research at the MS Society, said: "We urgently need therapies that can help slow the progression of MS and so we're delighted [...]

Immune System Boosted By Stem-Cell-Based Strategy In Mouse Model

Medical News Today, by Staff ~ May 20, 2013 Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, the tissue can be used to foster the development of white blood cells the body needs to mount healthy immune responses and to prevent harmful autoimmune reactions. The scientists who developed the thymus cells - which caused the proliferation and maturation of functioning immune cells when transplanted - said the achievement marks a significant step toward potential new treatments based on stem-cell and organ transplantation, as well as new therapies for type-1 diabetes and other autoimmune diseases, and for immunodeficiency diseases. Starting with human embryonic stem cells, UCSF researchers led by Mark Anderson, MD, PhD, an immunologist, and Matthias Hebrok, PhD, a stem-cell researcher and the director of the UCSF Diabetes Center, used a unique combination of growth factors to shape the developmental trajectory of the cells, and eventually hit upon a formula that yielded functional thymus tissue. The result, reported in the online edition of the journal Cell Stem Cell, is functioning tissue that nurtures the growth and development of the white blood cells known as T cells. T cells are a central immune cell population that responds to specific disease pathogens and also prevents the immune system from attacking the body's own tissues. The thymus might be a bit obscure to the layperson - it's a small gland at the top of the chest beneath the breastbone - but it is in no way expendable, as individuals with defective thymus function succumb to infection early in life. Given the invasive nature of cell therapy, [...]