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

Accumulated studies revealed that CD4(+)T cells were initially require d for diabetes in NOD mice, whereas interaction of CD4(+)T/CD8(+)T cel ls is not fully understood. To address this question, we established i slet-derived CD4(+)T cells and CD8(+)T cells from NOD mice. One NOD ne onate that received CD4(+)T cells developed diabetes and insulitis wit h CD8(+)T cells. Administration of cyclophosphamide to non-diabetic re cipients accelerated the development of diabetes, while none of the mi ce with anti-CD8 antibody did so. Similarly, it was observed that neon ates that received islet-derived CD8(+)T cells developed diabetes and obvious insulitis mainly with CD4(+)T cells. Administration of anti-CD 4 antibody with transfer of CD8(+)T cells inhibited insulitis. These r esults imply that CD8(+)T cells function as an initial element to recr uit CD4(+)T cells to islets as well as a final effector.