Activation of mixed glia by Abeta-specific Th1 and Th17 cells and its regulation by Th2 cells.
Microglia are innate immune cells of the CNS, that act as antigen-presenting cells (APC) for antigen-specific T cells and respond to inflammatory stimuli, such as amyloid-beta (Abeta), resulting in the release of neurotoxic factors and pro-inflammatory cytokines. Astrocytes can also act as APC and modulate the function of microglia. However, the role of distinct T cell subtypes, in particular Th17 cells, in glial activation and subsequent modulatory effects of Th2 cells are poorly understood. Here, we generated Abeta-specific Th1, Th2, and Th17 cells and examined their role in modulating Abeta-induced activation of microglia in a mixed glial culture, a preparation which mimics the complex APC types in the brain. We demonstrated that mixed glia acted as an effective APC for Abeta-specific Th1 and Th17 cells. Addition of Abeta-specific Th2 cells suppressed the Abeta-induced IFN-gamma production by Th1 cells and IL-17 production by Th17 cells with glia as the APC. Co-culture of Abeta-specific Th1 or Th17 cells with glia markedly enhanced Abeta-induced pro-inflammatory cytokine production and expression of MHC class II and co-stimulatory molecules on the microglia. Addition of Abeta-specific Th2 cells inhibited Th17 cell-induced IL-1beta and IL-6 production by mixed glia and attenuated Th1 cell-induced CD86 and CD40 expression on microglia. The modest enhancement of MHC class II and CD86 expression on astrocytes by Abeta-specific Th1 and Th17 was not attenuated by Th2 cells. These data indicate that Abeta-specific Th1 and Th17 cells induce inflammatory activation of glia, and that this is in part regulated by Th2 cells.
McQuillan
K
K
Trinity College Institute for Neuroscience, Trinity College, Dublin 2, Ireland.
Lynch
Marina A
MA
Mills
Kingston H G
KH
D000682:Amyloid / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001921:Brain / Q000166:cytology; D019013:CD40 Antigens / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D009457:Neuroglia / Q000145:classification / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000682:Amyloid; D051940:B7-2 Antigen; D019013:CD40 Antigens; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D007371:Interferon-gamma