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Microglial activation milieu controls regulatory T cell responses

Item Type:Article
Title:Microglial activation milieu controls regulatory T cell responses
Creators Name:Ebner, F. and Brandt, C. and Thiele, P. and Richter, D. and Schliesser, U. and Siffrin, V. and Schueler, J. and Stubbe, T. and Ellinghaus, A. and Meisel, C. and Sawitzki, B. and Nitsch, R.
Abstract:Although mechanisms leading to brain-specific inflammation and T cell activation have been widely investigated, regulatory mechanisms of local innate immune cells in the brain are only poorly understood. In this study, to our knowledge we show for the first time that MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia are potent inducers of Ag-specific CD4(+)Foxp3(+) regulatory T cells (Tregs) in vitro. Microglia differentially regulated MHC class II expression, costimulatory molecules, and IL-10 depending on the amount of IFN-{gamma} challenge and Ag dose, promoting either effector T cell or Treg induction. Microglia-induced Tregs were functionally active in vitro by inhibiting Ag-specific proliferation of effector T cells, and in vivo by attenuating experimental autoimmune encephalomyelitis disease course after adoptive transfer. These results indicate that MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia have regulatory properties potentially influencing local immune responses in the CNS.
Keywords:Brain, Cellular Microenvironment, Coculture Techniques, Cultured Cells, Experimental Autoimmune Encephalomyelitis, Forkhead Transcription Factors, Histocompatibility Antigens Class II, Immune Tolerance, Inbred C57BL Mice, Interferon-gamma, Interleukin-10, Lymphocyte Activation, Microglia, Regulatory T-Lymphocytes, T-Lymphocyte Subsets, Transgenic Mice, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:5594-5602
Date:1 December 2013
Official Publication:https://doi.org/10.4049/jimmunol.1203331
PubMed:View item in PubMed

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