MATURE MICROGLIA RESEMBLE IMMATURE ANTIGEN-PRESENTING CELLS

Owing to the difficulties of isolating adequate numbers of microglia f rom adult tissue, much of our understanding of their function is based on characterizations of microglia that develop in mixed glial culture s. To learn more about the nature of these cells in vivo, we have comp ared the phenotypes of murine microglia isolated from adults, neonates , and from mixed glial cultures with spleen cells from fetuses, neonat es, and adults. In the adult CNS, the only resident population of cell s that express CD45, a protein tyrosine phosphatase, are the F4/80(+) and FcR(+) cells: the microglia. In contrast to all other differentiat ed cells of hemopoietic origin, microglial CD45 levels fail to increas e from the neonatal period through adulthood. Rather, their levels are indistinguishable from the low levels found on a small population of embryonic day 16 liver cells. Conversely, we find that the F4/80 value s of microglia are elevated as compared to splenic macrophages. Striki ngly, microglia that develop in mixed glial cultures display a more ac tivated phenotype, with low F4/80 values, weak MHC class II expression , and the appearance of a subset of cells positive for the dendritic c ell marker, NLDC145. Additionally CD45 values are elevated to a level intermediate between that of adult microglia and adult spleen, a level similar to that found on microglia activated in vivo. Consistent with this activated phenotype, indomethacin revealed the ability of mixed glial culture microglia to present a peptide antigen to naive T-cells expressing a defined T-cell receptor. Although adult microglia did exp ress costimulatory molecules, B7.2, ICAM-1, and CD40, and could be ind uced to express MHC class II, they failed to present antigen in the sa me assay. Interestingly, these same cells could stimulate T-cell proli feration in a mixed lymphocyte reaction but not in an allogeneic speci fic manner. Taken together these data suggest that adult microglia rem ain in a relatively immature and unactivated state of differentiation as compared to other tissue macrophages. (C) 1998 Wiley-Liss, Inc.