LYMPHOCYTE SUBSETS IN THYMUS AND PERIPHERAL LYMPHOID-TISSUES OF AGINGAND DIABETIC NOD MICE

The nonobese diabetic (NOD) mouse spontaneously develops insulin depen dent diabetes mellitus. The disease is associated with a leucocytic in filtration of the pancreatic islets of Langerhans and it is believed t hat during the development of autoimmune diabetes, the insulin-secreti ng islet beta-cells are destroyed by autoreactive T lymphocytes. We in vestigated the alteration of lymphocyte subsets in central and periphe ral lymphoid organs of NOD female mice with increasing age beginning b efore the onset of insulitis and ending well after the onset of diabet es. The spleen, inguinal and pancreatic lymph nodes all increased in c ell number, especially after the onset of insulitis (8 weeks), and all decreased after the onset of diabetes. Flow cytometric studies showed a widening of the visible side scatter profile of female NOD lymph no de cells which coincided with the initiation of insulitis. Anti-CD4 an d anti-CD8 double staining of thymocytes revealed a large increase in the double negative population and a corresponding decrease in the dou ble positive population, but this occurred long after the onset of dia betes. Generally, there was an increase in the CD4 : CD8 ratio in the peripheral lymphoid organs during the onset of insulitis which was lar gely due to an increase in the CD4 T cell population while the ratio d ecreased after the onset of diabetes. In the spleen this was mostly du e to an increase in CD8 T cells. The pancreatic lymph nodes, which the oretically might reflect what is happening in the pancreas, showed an unexpected decrease in overall cell number and a decrease in T-cells ( especially CD4 T cells), while B cells were increased. Overall, it wou ld appear that no single immunological parameter could be used to pred ict a prediabetic state.