title: Microglial activation milieu controls regulatory T cell responses.
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-γ 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.
authors.affiliation: Institute for Cell Biology and Neurobiology, Charité-University Medicine Berlin, 10117 Berlin, Germany;
authors.forename: Friederike
authors.initials: F
authors.lastname: Ebner
authors.forename: Christine
authors.initials: C
authors.lastname: Brandt
authors.forename: Peggy
authors.initials: P
authors.lastname: Thiele
authors.forename: Daniel
authors.initials: D
authors.lastname: Richter
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schliesser
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.forename: Jutta
authors.initials: J
authors.lastname: Schueler
authors.forename: Tobias
authors.initials: T
authors.lastname: Stubbe
authors.forename: Agnes
authors.initials: A
authors.lastname: Ellinghaus
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Birgit
authors.initials: B
authors.lastname: Sawitzki
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10; D007371:Interferon-gamma