Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide accumulate in the pancreas and contribute to disease pathogenesis in nonobese diabetic mice

We previously reported a peptide KS20 from islet amyloid polypeptide (IAPP) to be the target Ag for a highly diabetogenic CD4 T cell clone BDC-5.2.9. To track IAPP-reactive T cells in NOD mice and determine how they contribute to the pathogenesis of type 1 diabetes, we designed a new I-Ag7 tetramer with high affinity for BDC-5.2.9 that contains the peptide KS20. We found that significant numbers of KS20 tetramer(+) CD4 T cells can be detected in the pancreas of prediabetic and diabetic NOD mice. To verify pathogenicity of IAPP-reactive cells, we sorted KS20 tetramer(+) cells and cloned them from uncloned T cell lines isolated from spleen and lymph nodes of diabetic mice. We isolated a new KS20-reactive Th1 CD4 T cell clone that rapidly transfers diabetes. Our results suggest that IAPP triggers a broad autoimmune response by CD4 T cells in NOD mice.