Chronically stimulated microglial cells do no longer alter their immune functions in response to the phagocytosis of apoptotic cells.
In an autoimmune inflammatory setting, ingestion of apoptotic T cells leads to a down-regulation of microglial immune functions. Recent studies have indicated that microglia can be matured by exposure to GM-CSF. GM-CSF stimulation led to a differentiated microglial phenotype and enhanced antigen-presenting capabilities. The secretion of TNF-alpha was significantly decreased by the uptake of apoptotic cells in unstimulated microglia, but not in GM-CSF-differentiated microglia. IL-10 secretion was unaffected. After ingestion of apoptotic cells, only previously unstimulated, but not GM-CSF-differentiated microglial cells decreased their T cell-activating potential as measured by IFN-gamma secretion in antigen-activated MBP-specific T cells. Thus, GM-CSF stimulation reduces the immunomodulatory functions of microglial cells.
Magnus
Tim
T
Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Homburg, D-66421 Homburg/Saar, Germany. netmag@uniklinik-saarland.de
Korn
Thomas
T
Jung
Stefan
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004660:Encephalitis / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor