ESTROGEN INFLUENCES CD4(-LYMPHOCYTE ACTIVITY IN-VIVO AND IN-VITRO IN BETA(2)-MICROGLOBULIN-DEFICIENT MICE() T)

Oestrogen directly influences autoimmune diseases and the immune respo nse to microbes. We studied the effect of oestrogen on CD4+ T cells sp ecific for lymphocytic choriomeningitis virus (LCMV) using mice geneti cally engineered to be deficient in beta(2)-microglobulin (beta(2)m(-/ -)). These mice are deficient in beta(2)-microglobulin, class I major histocompatibility complex (MHC) molecules and CD8+ T lymphocytes. Fat al leptomeningitis after intracranial infection with LCMV is mediated by CD8+ cytotoxic T lymphocytes (CTL) in wild-type C57BL/6 mice, and b y CD4+ T cells in beta(2)m(-/-) mice. Male and female wild-type C57BL/ 6 mice showed equal susceptibility to immune meningitis. In contrast, male beta(2)m(-/-) mice were less susceptible to fatal immune meningit is than were females. Orchidectomy and oestrogen treatment of male bet a(2)m(-/-) mice in vivo restored susceptibility to meningitis. The cla ssic weight loss seen in beta(2)m(-/-) mice after intracranial infecti on was also accentuated in females. Further, the in vitro activity of CD4(+) T cells from male beta(2)m(-/-) mice, as measured by CTL assays , was shown to be dependent on oestrogen. The natural killer cell acti vity of spleen cells from beta(2)m(-/-) mice after infection with LCMV was not affected by oestrogen. These data demonstrate the influence o f oestrogen on CD4(+) T-cell activity both in vivo and in vitro.