T Cells in the Pathogenesis of Type 1 Diabetes

T lymphocytes' crucial role in the autoimmune process leading to insulin-dependent type 1 diabetes is now universally recognized. Research focuses on identifying pathogenic and nonpathogenic T cells, understanding how they are primed and expanded, characterizing their antigen specificity, and ultimately on devising strategies to blunt their autoaggressive action. In this review, we focus on recent progress identified in three different areas. Results obtained with transgenic mice acknowledge proinsulin's unique role in triggering autoimmunity and suggest that other beta-cell proteins are recognized as a result of epitope spreading, at least in the nonobese diabetic mouse. Progress has also been achieved by developing and validating reliable CD4(+) and CD8(+) T-cell tests that may prove valuable for diagnostic and prognostic purposes in the near future. Finally, recent results provide novel and important guidance for manipulating autoreactive T-cell responses against beta-cell antigens.