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.
Cash
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INSERM U283, Cochin Hospital, Paris, France.
Rott
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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