PMID- 9436789 OWN - NLM STAT- MEDLINE DCOM- 19980226 LR - 20220309 IS - 0894-1491 (Print) IS - 0894-1491 (Linking) VI - 22 IP - 1 DP - 1998 Jan TI - Mature microglia resemble immature antigen-presenting cells. PG - 72-85 AB - Owing to the difficulties of isolating adequate numbers of microglia from adult tissue, much of our understanding of their function is based on characterizations of microglia that develop in mixed glial cultures. To learn more about the nature of these cells in vivo, we have compared the phenotypes of murine microglia isolated from adults, neonates, and from mixed glial cultures with spleen cells from fetuses, neonates, and adults. In the adult CNS, the only resident population of cells that express CD45, a protein tyrosine phosphatase, are the F4/80+ and FcR+ cells: the microglia. In contrast to all other differentiated cells of hemopoietic origin, microglial CD45 levels fail to increase 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 values of microglia are elevated as compared to splenic macrophages. Strikingly, microglia that develop in mixed glial cultures display a more activated phenotype, with low F4/80 values, weak MHC class II expression, and the appearance of a subset of cells positive for the dendritic cell 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 express costimulatory molecules, B7.2, ICAM-1, and CD40, and could be induced to express MHC class II, they failed to present antigen in the same assay. Interestingly, these same cells could stimulate T-cell proliferation in a mixed lymphocyte reaction but not in an allogeneic specific manner. Taken together these data suggest that adult microglia remain in a relatively immature and unactivated state of differentiation as compared to other tissue macrophages. FAU - Carson, M J AU - Carson MJ AD - Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. FAU - Reilly, C R AU - Reilly CR FAU - Sutcliffe, J G AU - Sutcliffe JG FAU - Lo, D AU - Lo D LA - eng GR - AI31583/AI/NIAID NIH HHS/United States GR - AI38375/AI/NIAID NIH HHS/United States GR - MH47680/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - EC 3.1.3.48 (Leukocyte Common Antigens) RN - XXE1CET956 (Indomethacin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Antigen-Presenting Cells/drug effects/*immunology MH - Bone Marrow Cells/physiology MH - Brain/cytology MH - Cells, Cultured MH - Flow Cytometry MH - Indomethacin/pharmacology MH - Leukocyte Common Antigens/metabolism MH - Lymphocytes/metabolism MH - Macrophages, Alveolar/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microglia/drug effects/*immunology MH - Phenotype MH - Spleen/cytology EDAT- 1998/01/22 18:05 MHDA- 2000/06/20 09:00 CRDT- 1998/01/22 18:05 PHST- 1998/01/22 18:05 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1998/01/22 18:05 [entrez] AID - 10.1002/(SICI)1098-1136(199801)22:1<72::AID-GLIA7>3.0.CO;2-A [pii] AID - 10.1002/(sici)1098-1136(199801)22:1<72::aid-glia7>3.0.co;2-a [doi] PST - ppublish SO - Glia. 1998 Jan;22(1):72-85. doi: 10.1002/(sici)1098-1136(199801)22:1<72::aid-glia7>3.0.co;2-a.