CD8(+) T cells specific for beta cells encounter their cognate antigens in the islets of NOD mice.

CD8(+) T cells play a key role in the initiation of insulitis. However, the site(s) where naive CD8(+) T cells encounter beta-cell antigens and the mechanism(s) by which beta-cell autoimmunity is initiated remain to be determined. In the current study, an adoptive transfer model was employed assessing the initial site of priming and the nature of antigen recognition by naive beta-cell-specific CD8(+) T cells. Temporal analysis demonstrated that unlike CD4(+) T cells that are primed in the draining pancreatic lymph nodes, initial proliferation of transferred CD8(+) T cells was detected in the islets. These results indicate that in our model, naive beta-cell-specific CD8(+) T cells encounter beta-cell antigens in the islets. Furthermore, ectopic expression of CD80 by beta cells accelerated the onset of insulitis mediated by beta-cell-specific CD8(+) T cells, but had no effect on CD4(+) T-cell-mediated diabetes, suggesting an antigenic interaction between beta cells and naive CD8(+) T cells. However, it remains to be determined whether the initiation of insulitis in spontaneous diabetes is the result of a cognate interaction between naive CD8(+) T cells and islet beta cells.