T-cell Tolerance and Autoimmune Diabetes

Abstract

Herein we describe the major signaling events that occur in T-cells upon T-cell receptor (TCR) engagement, and the mechanisms responsible for the induction of T-cell anergy that may ultimately lead to the development of immunospecific therapies in T-cell mediated autoimmune diseases. A new type of antigen presenting molecule (dimeric MHC class-II/peptide, DEF) endowed with antigen-specific immunomodulatory effects such as induction of Th2 polarization and T-cell anergy is also described as a potential antidiabetogenic agent. According to our preliminary results, the MHC II/peptide-based approach may provide rational grounds for further development of antigen-specific immunotherapeutic agents such as human-like MHC II/peptide chimeras endowed with efficient down-regulatory effects in CD4 T-cell-mediated autoimmune diseases such as Type 1 diabetes, multiple sclerosis, primary biliary cirrhosis, and rheumatoid arthritis.

Key Words:

• TCR/CD4 signaling
• T-cell tolerance
• Insulin-dependent diabetes mellitus
• Recombinant MHC II-peptide chimera