Effect of 5-alpha dihydrotestosterone on T-cell proliferation of the female nonobese diabetic mouse.

Nonobese diabetic (NOD) mice develop type I diabetes spontaneously and have been utilized as a model for human autoimmune insulin-dependent diabetes. The disease is caused by the destruction of insulin-producing p cells in the pancreatic islet of Langerhans by infiltrating inflammatory cells, which are primarily T lympho- cytes. The incidence of diabetes in NOD mice is increased in females compared with males, suggesting that sex steroid hormones play an important role in the develop- ment of the disease. We therefore investigated the effect of a male steroid, 5-a- dihydrotestosterone (5DHT), on disease development, T-cell phenotype, T-cell prolif- eration, and cytokine profiles in this model. None of the mice that received 5DHT for 120 days (n = 7) developed insulitis, whereas all control mice (n = 8) developed the disease. The percentage of CD4+ T cells in peripheral blood mononuclear cells was markedly decreased in the 5DHT-treated females compared with those in controls (37.1 -e 4.8 vs 51.3 f 9.3, P < 0.02), whereas no significant differences in the percent- age of CD8+ T cells were observed between treated and control female mice. Results of a syngeneic mixed lymphocyte reaction (SMLR) also suggested that T cells are major target cells of 5DHT administration. An increased expression of IL-4 mRNA, representing T helper 2 (Th2) T cells, was observed in the SMLR. On the basis of these results, a systemic administration of 5DHT appears to have direct effects on the expansion of Th2 cell populations with subsequent restoration of normal immune responses. (P.S.E.B.M. 1996, Vol213)