THE ROLE OF NK CELL-ACTIVITY IN THE PATHOGENESIS OF POLY I-C ACCELERATED AND SPONTANEOUS DIABETES IN THE DIABETES-PRONE BB RAT

The development of insulin dependent diabetes mellitus (IDDM) and diab etes in the diabetes prone (DP) BE rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have be en implicated but not proven to play a pathogenetic role in BE rats du e to the increased NK cell number and activity found in these animals. We have recently reported that poly I:C, an inducer of cytokines and a potent enhancer of NK cell function, accelerates the development of diabetes in DP BE rats and induces diabetes in diabetes resistant (DR) BE rats. Since we have further demonstrated that poly I:C administrat ion to BE rats increases NK cell number and levels of inducers of NK c ell activity, interferon-alpha and IL-6 which is described therein, we tested the hypothesis that NK cell activity plays an important role i n poly I:C accelerated disease. The role of NK cells in poly I:C accel erated diabetes and spontaneous diabetes was examined by determining w hether selective depletion of NK cells using a rat NK cell specific an tibody (anti-NKR-P1 antibody) alters the development of diabetes. The treatment of BE rats with anti-NKR-P1 antibody resulted in a significa ntly lower mean NK cell activity of splenic mononuclear cells than tha t found in control animals. However, the development of diabetes and d egree of insulitis was not significantly different between treatment g roups. BE rats administered anti-NKR-P1 antibody with poly I:C had a l ower mean splenocyte NK cell activity and lower mean Mt cell number wi thin the peripheral blood and inflamed islets than rats administered p oly I:C alone. However, anti-NKR-P1 antibody administration did not al ter the accelerated development of diabetes or the degree of insulitis in poly I:C treated animals. These data document that not play a majo r role in the pathogenesis of poly I:C accelerated diabetes or spontan eous diabetes in the DP BE rat. (C) 1995 Academic Press Limited