SummaryMicroglia, a type of tissue macrophage, are the only cells in the central nervous system (CNS) parenchyma to express some major histocompatibility complex (MHC) class II constitutively or to upregulate expression readily. They are thought to play a role in CD4 T cell activation in autoimmune diseases such as multiple sclerosis, as well as in neurodegenerative conditions, Alzheimer's disease in particular. We show here that highly purified MHC class II + microglia when tested directly ex vivo do indeed support an effector response by an encephalitogenic myehn basic protein-reactive CD4 T cell line from which production of the proinflammatory cytokines, interferon ~/and tumor necrosis factor, is elicited, but not interleukin (IL)-2 secretion or proliferation. After this interaction, the T cells die by apoptosis. Other nonmicroglial but CNS-associated macrophages isolated in parallel stimulate full T cell activation, Including IL-2 production, proliferation, and support T cell survival. Neither CNS-derived population expresses BT.1/B7.2. Resident macrophages that terminate effector T cells in tissues constitute a novel and broadly applicable regulatory measure of particular relevance to processes of selftolerance against sequestered antigens.

Lymphotoxin (LT)‐α, a member of the TNF family, is recognized as an important mediator in different aspects of lymphoid organ development. Targeted disruption of this molecule resulted in a substantial reduction in the proportion of αEβ7‐integrinhigh CD8+ T cells detectable in peripheral lymphoid organs. This defect, however, was not observed on mature CD4–CD8+ thymocytes. To determine whether this was due to downregulation of β7‐integrin expression by peripheral CD8+ T cells or a failure of thymic emigration of CD8+ β7‐integrinhigh T cells, β7‐integrin was examined on recent thymic emigrants (RTE). When analysed within 16 h after leaving the thymus CD4–CD8+ RTE in both LT‐α–/– and wild type (wt) mice remained β7‐integrinhigh and were indistinguishable. However, within 3–5 days, emigration loss of β7‐integrin became evident in LT‐α–/– mice. Despite this loss, the proportion of thymically derived αβTCR+ T‐cell populations in the intestinal epithelium, an important target tissue of CD8+ αEβ7‐integrinhigh T cells, was increased in the absence of LT‐α. In contrast, B cells were detectable only rarely in the intestinal tissue of LT‐α–/– mice. The expression of E‐Cadherin remained unchanged. These results indicate that a LT‐α‐dependent process maintains a high level of αEβ7‐integrin expression by peripheral CD8+ T cells, and with this control mechanism LT‐α may help to regulate CD8+ T‐cell numbers in the tissues.