PRESENTATION OF BETA-CELL ANTIGENS TO CD4-CELLS OF NONOBESE DIABETIC MICE( AND CD8+ T)

We isolated CD4+ and CD8+ T cell clones from pancreatic islets of non- obese diabetic (NOD) mice and studied their interactions with pancreat ic islets, in culture. The three CD4+ T cell clones proliferated when cultured with islet cells from NOD, BALB/c, or C57BL/6 (B6) mice. For proliferation to the allogeneic islets, however, APC from NOD mice wer e required in the culture. Two of the clones also produced IFN-gamma u pon culture with NOD islet cells. The Ag from islet cells responsible for T cell stimulation were not released into the supernatant but were cell associated. Paraformaldehyde treatment of islet cells, in fact, preserved their antigenicity. The fixed islet cells could present Ag t o CD4+ T cell clones, provided live, syngeneic APC were added to the c ulture. We conclude from these experiments that islet cells donate Ag to the APC for presentation and that the function of APC is to process the Ag. The two CD8+ T cell clones proliferated and released IFN-gamm a upon reaction with islet cells from either NOD or BALB/c but not B6 mice. The CD8+ T cell clones also reacted with the insulinoma NIT-1 ce ll line, derived from NOD mice. Fixation of NIT-1 cells did not impair recognition when live APC were present in the culture. In this case, however, the APC could be allogeneic. We conclude that CD8+ T cells di rectly recognized a MHC class I-restricted Ag on target cells, but nee ded the costimulatory effect of APC. We also found that CD8+ T cells k illed islet cells. Two of the CD4+ T cell clones produced diabetes whe n transferred into male, irradiated NOD mice. For optimal transfer of disease, the CD4+ T cell clones had to be co-injected with CD8+ T cell s from NOD diabetic mice. The two CD8+ T cell clones did not transfer disease.