A NOVEL FUNCTION OF ISLET-DERIVED CD8(+)T CELLS IN INITIATING AND DEVELOPING AUTOIMMUNE INSULIN-DEPENDENT DIABETES-MELLITUS IN NONOBESE DIABETIC (NOD) MICE

Accumulated studies revealed that CD4(+)T cells were initially required for diabetes in NOD mice, whereas interaction of CD4(+)T/CD8(+)T cells is not fully understood. To address this question, we established islet-derived CD4(+)T cells and CD8(+)T cells from NOD mice. One NOD neonate that received CD4(+)T cells developed diabetes and insulitis with CD8(+)T cells. Administration of cyclophosphamide to non-diabetic recipients accelerated the development of diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was observed that neonates that received islet-derived CD8(+)T cells developed diabetes and obvious insulitis mainly with CD4(+)T cells. Administration of anti-CD4 antibody with transfer of CD8(+)T cells inhibited insulitis. These results imply that CD8(+)T cells function as an initial element to recruit CD4(+)T cells to islets as well as a final effector.