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Alloantigen presentation to naive CD8 + T cells by mouse microglia: Evidence for a distinct phenotype based on expression of surface‐associated and soluble costimulatory molecules
Author(s) -
Askew David,
Walker William S.
Publication year - 1996
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199610)18:2<118::aid-glia4>3.0.co;2-x
Subject(s) - biology , phenotype , microglia , cd8 , microbiology and biotechnology , immunology , neuroscience , cytotoxic t cell , immune system , genetics , in vitro , gene , inflammation
We previously showed that approximately one‐third of mouse primary microglial clones derived from individual precursor cells residing in normal brain constitutively present alloantigens (alloAgs) to naive CD8?? T cells (Moore et al.: J Neuroimmunol 41:203, 1992). To understand the basis for this alloAg presenting (alloAgP) activity, we developed a panel of microglial cell lines that were characterized by patterns of alloAgP activity similar to that of the primary clones. Flow cytometric analysis revealed that microglia with and without alloAgP activity expressed similar levels of major histocompatibility complex class I molecules; however, CD80 (B7‐1) and CD86 (B7‐2) expression was primarily restricted to the alloAgP?? cell lines. Monoclonal antibody (Mab) to CD80 only partially blocked the proliferative response of allogeneic CD8?? T cells cocultured with the presenting cell lines, whereas Mab to CD86 completely inhibited the response, indicating a significant role for this molecule in T‐cell activation. Using an immunoassay, recombinant mouse cytokines, cytokine‐specific Mabs, and the reverse transcriptase‐polymerase chain reaction to detect specific cytokine mRNAs, we found the synthesis of interleukin (IL)‐1α, IL‐6, IL‐12, and tumor necrosis factor‐α (TNF‐α) to be restricted to the alloAgP?? cell lines. Costimulatory roles were then identified for these molecules. We conclude that the ability to present alloAg is a property of a subset of microglia that constitutively express CD86 and secrete costimulatory cytokines that promote the expansion of the alloAg‐stimulated CD8?? T cells. © 1996 Wiley‐Liss, Inc.