The transfer of autoimmune diabetes in NOD mice can be inhibited or accelerated by distinct cell populations present in normal splenocytes taken from young males.
The NOD mouse is characterized by the development of spontaneous autoimmune diabetes which begins with a peri-islet lymphocyte infiltration of the pancreas around 6 weeks of age and progresses to overt diabetes in 50-60% of females from about 12 weeks. Although infiltration occurs around islets in males, the incidence of overt diabetes is much less (about 1%) and suggests that there may be more effective regulatory circuits in these animals. This possibility was examined by using splenocytes from young males to reconstitute irradiated male recipients 6 d before the transfer of diabetogenic spleen cells from spontaneously diabetic females. Those animals which were not reconstituted with male spleen cells developed diabetes 3-5 weeks later, whereas the majority of the reconstituted mice remained normoglycaemic. Characterization of the protective population demonstrated a role for CD4+ T cells. An additional observation was that splenocytes from young normal males also contained a population of non-T cells which could advance the diabetogenic transfer of disease by at least a week.