The immune tolerance network--an NIH/JDF-supported initiative to bring tolerance research into the clinic: a major new resource for clinical immunologists.

Abstract

The prevalence of immune-mediated diseases in the United States, and indeed, around the world, is a significant health care problem that requires an aggressive and innovative approach to the development of new treatment solutions. Immune-mediated diseases include a broad spectrum of autoimmune diseases, such as rheumatoid arthritis, diabetes mellitus, lupus, and multiple sclerosis, as well as conditions in which excessive reactivity to exogenous agents causes asthma and various allergic diseases. These diseases affect tens of millions of Americans and result in annual medical and other indirect costs of over $100 billion. Furthermore, immune-mediated graft rejection impacts over 20,000 Americans suffering from nonimmunologic diseases who receive organ transplants each year. Over the past 40 years, improved results in the treatment of immune-mediated diseases have been achieved primarily through the development of increasingly potent nonspecific immunosuppressive drugs that inhibit immune responses. Immunotherapies, such as steroids, cyclosporin A, and pan-reactive monoclonal antibodies have met with a degree of clinical success in treating conditions such as acute immune rejection of organ transplants and severe autoimmune diseases. However, such therapies require life-long usage and nonspecifically suppress the entire immune system, exposing patients to considerably higher risks of infection. Additionally, many of these therapies increase the risk of cancer. Thus, a major goal for treatment of immune disorders is the induction of immune tolerance—selective short-term immunotherapy targeted at eliminating only the pathogenic immune response while preserving normal, beneficial immune function. The advances in the development of tolerogenic strategies in clinical transplantation have been fueled by extensive basic research advances that have increased our conceptual understanding of the mechanisms operative in the induction of tolerance and restoration of self-tolerance. In addition, multiple