Regulation of microglia by CD4+ and CD8+ T cells: Selective analysis in CD45-congenic normal and Toxoplasma gondii-infected bans marrow chimeras

Microglia, the resident macrophage population of the central nervous system , is rapidly activated in murine Toxoplasma encephalitis (TE). However, the precise contribution of microglia to intracerebral immune reactions and th e in vivo regulation of microglial activity are still poorly understood. To selectively analyse microglial reactions in TE, we have established a mode l of radiation-induced CD45-congenic bone marrow chimeras between CD45.2(+) C57BL/6 (recipient) and CD45.1(+) B6.SJL (donor) mice. These chimeras allo w a differentiation of radioresistant CD45.2(+) microglia from all other le ukocytes, which exhibit the CD45.1(+) haplotype, in the normal brain, micro glia produced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, I L-10, and IL-15 mRNA. In TE, marked microglial activation was observed with a de novo expression of IL-12p40 and inducible nitric oxide synthase mRNA, upregulation of IL-1 beta and TNF-alpha mRNA, a continuous production of I L-10, and IL-15 mRNA, an induction of major histocompatibility class I and II antigens, intercellular adhesion molecule-1,and leukocyte function-assoc iated antigen-1. Furthermore, selective depletion of CD4(+) and/or CD8(+) T cells in the chimeras revealed that microglial cytokine production was cri tically regulated by CD8(+) T cells, whereas expression of cell surface mol ecules was less dependent on T cells. These findings demonstrate a specific regulation of microglia by T lymphocytes during the course of TE.