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

Abstract

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 the in vivo regulation of microglial activity are still poorly understood. To selectively analyse microglial reactions in TE, we have established a model of radiation-induced CD45-congenic bone marrow chimeras between CD45.2+ C57BL/6 (recipient) and CD45.1+ B6.SJL (donor) mice. These chimeras allow a differentiation of radioresistant CD45.2+ microglia from all other leukocytes, which exhibit the CD45.1+ haplotype. In the normal brain, microglia produced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-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-1beta and TNF-alpha mRNA, a continuous production of IL-10, and IL-15 mRNA, an induction of major histocompatibility class I and II antigens, intercellular adhesion molecule-1, and leukocyte function-associated antigen-1. Furthermore, selective depletion of CD4+ and/or CD8+ T cells in the chimeras revealed that microglial cytokine production was critically regulated by CD8+T cells, whereas expression of cell surface molecules was less dependent on T cells. These findings demonstrate a specific regulation of microglia by T lymphocytes during the course of TE.