Effective and selective immune surveillance of the brain by MHC class I‐restricted cytotoxic T lymphocytes

Cytotoxic CD8+ T cells are abundantly present in human virus‐induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8+ T cell‐mediated brain inflammation by transferring MHC class I‐restricted hemagglutinin (HA)‐reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8+ T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4+ cells, brain inflammation peaks after 5–7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4+ cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen‐containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4+ T cells, some CD8+ cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8+ T cells areprime candidates for immune surveillance of the CNS.