MICROGLIA INDUCE CD4 T-LYMPHOCYTE FINAL EFFECTOR FUNCTION AND DEATH

Microglia, a type of tissue macrophage, are the only cells in the cent ral nervous system (CNS) parenchyma to express some major histocompati bility complex (MHC) class II constitutively or to upregulate expressi on readily. They are thought to play a role in CD4 T cell activation i n autoimmune diseases such as multiple sclerosis, as well as in neurod egenerative conditions, Alzheimer's disease in particular. We show her e that highly purified MHC class II+ microglia when tested directly ex vivo do indeed support an effector response by an encephalitogenic my elin basic protein-reactive CD4 T cell line from which production of t he proinflammatory cytokines, interferon gamma and tumor necrosis fact or, is elicited, but not interleukin (IL)-2 secretion or proliferation . After this interaction, the T cells die by apoptosis. Other nonmicro glial but CNS-associated macrophages isolated in parallel stimulate fu ll T cell activation, including IL-2 production, proliferation, and su pport T cell survival. Neither CNS-derived population expresses B7.1/B 7.2. Resident macrophages that terminate effector T cells in tissues c onstitute a novel and broadly applicable regulatory measure of particu lar relevance to processes of self-tolerance against sequestered antig ens.