ASSOCIATION BETWEEN ALPHA-BETA-TCR(-)CD8(-) T-CELL DEFICIENCY AND IDDM IN NOD()CD4()LT MICE/

NOD mice develop spontaneous IDDM as a result of T-cell-mediated autoi mmune destruction of pancreatic beta-cells. It is not known why these T-cells become autoreactive, nor is it clear whether the breakdown in self-tolerance reflects a general problem in T-cell development or a s elective defect in an as yet undefined regulatory cell population. In this study, we showed that NOD mice, although relatively normal with r egard to most thymocyte subsets, exhibit a marked deficiency in alpha beta TCR(+)CD4(-)CD8(-) (alpha beta(+)DN) T-cells in the thymus and, t o a lesser extent, in the periphery. These T-cells have been termed NK T cells (NK1.1(+)-like T-cells) because they share some cell surface m arkers with conventional natural killer (NK) cells. To examine the rol e of these cells in the pathogenesis of IDDM, semiallogeneic or syngen eic double-negative (DN) thymocytes, enriched for NKT cells, were tran sferred into intact 4-week-old NOD recipients; the onset of diabetes w as then monitored over the ensuing 30 weeks. Mice receiving NKT-enrich ed thymocytes did not develop diabetes, whereas mice receiving unfract ionated thymocytes or phosphate-buffered saline developed diabetes at the normal rate. NKT cells represent a distinct T-cell lineage that ha s been shown to play a role in immunoregulation in vivo. The deficienc y of these cells observed in NOD mice may therefore contribute to dest ruction of pancreatic islet cells by conventional T-cells.