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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.
Baker RL, Delong T, Barbour G, Bradley B, Nakayama M, Haskins K
Abstract:
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
.
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
.
