Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+ T lymphocytes in the central nervous system.
The potential of central nervous system (CNS)-derived cells for initiating T cell responses is not known. Using the capacity of unprimed T cells to respond to allogeneic determinants on antigen-presenting cells (APC), we assessed the ability of microglial cells to act as stimulators of primary T cell responses in vitro. For this purpose, microglial cells were activated with lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), or by phagocytosis of progenitor oligodendrocytes and subsequently tested for their ability to induce a proliferative response of naive, resting T cells. Activated microglial cells induced a significant proliferation of virgin, alloreactive CD4+ and CD8+ T lymphocytes, with a more substantial response of highly purified CD4+ than of CD8-expressing T cells. Phagocytosis activation was the most efficient stimulus to induce this APC competence on microglial cells. By contrast, IFN-gamma-pretreated, MHC-expressing astrocytes were unable to induce similar responses of alloreactive CD4+ or CD8+ T cells under the same experimental conditions. Collectively, our data suggest the role of activated microglia as the fully immunocompetent accessory cell population of the CNS.
INSERM U283, Cochin Hospital, Paris, France.
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D000818:Animals; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D017628:Microglia / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
D007519:Isoantigens; D007371:Interferon-gamma