T-lymphocyte recognition of beta cells in type 1 diabetes: clinical perspectives

Type 1 diabetes (T1D) is an autoimmune disease characterized by the activation of lymphocytes against pancreatic β cells. Landmarks in the history of T1D were the description of insulitis and of islet cell autoantibodies, and report an association between T1D and a limited number of HLA alleles. Another step was the study of T-lymphocytes, now known to be central to the disease process of T1D whether in mice or men. In humans, T-lymphocytes, and especially CD8⁺ T-cells, are predominant in insulitis. The characterization of antigenic fragments--peptides--recognized by T-cells paves the way towards new assays for predicting T1D and its prevention using antigen- or peptide-specific immunotherapy, while avoiding side effects that may counteract the limited efficacy of immunosuppression and immunomodulation in preserving β-cells from autoimmune destruction in recent-onset T1D patients. The current need for new preclinical models for testing strategies of antigen-specific immune tolerance is also highlighted.