Immunomodulatory Strategies and GAD65 Therapy in Type 1 Diabetes

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic cells by the autoimmune system, which is common in children and adolescents. Current treatment still mainly relies on exogenous insulin, which is difficult to achieve a radical cure and cannot prevent the progression of the disease. Therefore, the development of immunomodulatory therapies targeting the cause has become a research focus. This article systematically reviews the pathogenesis and typical symptoms of T1D, focusing on the analysis of immunomodulatory treatment strategies including anti-CD3 monoclonal antibodies (such as teplizumab), low-dose IL-2, and anti-TNF-, and their efficacy in regulating autoreactive T cells and inducing regulatory T cells. The article specifically discusses antigen-specific treatments targeting GAD65, such as GAD-alum immunotherapy, which has shown the potential to protect residual cell function in people with specific genetic backgrounds (such as HLA-DR3-DQ2). Mechanistic studies have shown that GAD65 treatment can induce Th2 and Treg immune deviations and inhibit inflammatory responses. Despite the limitations of efficacy differences and individual responses, GAD65-related therapies have broad prospects in the context of precision medicine and are expected to serve as an effective supplement for the treatment of T1D.