Mechanistic basis of immunotherapies for type 1 diabetes mellitus.
Type 1 diabetes (T1D) is an autoimmune disease for which there is no cure. The pancreatic beta cells are the source of insulin that keeps blood glucose normal. When susceptible individuals develop T1D, their beta cells are destroyed by autoimmune T lymphocytes and no longer produce insulin. T1D patients therefore depend on daily insulin injections for survival. Gene therapy in T1D aims at the induction of new islets to replace those that have been destroyed by autoimmunity. A major goal of T1D research is to restore functional beta cell mass while eliminating diabetogenic T cells in the hope of achieving insulin independence. Multiple therapeutic strategies for the generation of new beta cells have been under intense investigations. However, newly formed beta cells would be immediately destroyed by diabetogenic T cells. Therefore, successful islet induction therapy must be supported by potent immunotherapy that will protect the newly formed beta cells. Herein, we will summarize the current information on immunotherapies that aim at modifying T cell response to beta cells. We will first outline the immune mechanisms that underlie T1D development and progression and review the scientific background and rationale for specific modes of immunotherapy. Numerous clinical trials using antigen-specific strategies and immune-modifying drugs have been published, though most have proved too toxic or have failed to provide long-term beta cell protection. To develop an effective immunotherapy, there must be a continued effort on defining the molecular basis that underlies T cell response to pancreatic islet antigens in T1D.
Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Wenhao
W
Chen
Aini
A
Xie
Lawrence
L
Chan
D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology