6533b82dfe1ef96bd1291563

RESEARCH PRODUCT

Microglial activation milieu controls regulatory T cell responses.

Ulrike SchliesserAgnes EllinghausDaniel RichterChristine BrandtChristian MeiselPeggy ThieleRobert NitschTobias StubbeBirgit SawitzkiJutta SchuelerVolker SiffrinFriederike Ebner

subject

Encephalomyelitis Autoimmune ExperimentalRegulatory T cellT cellImmunologychemical and pharmacologic phenomenaMice TransgenicLymphocyte ActivationT-Lymphocytes RegulatoryImmune toleranceInterferon-gammaMiceImmune systemT-Lymphocyte SubsetsmedicineImmune ToleranceImmunology and AllergyAnimalsCells CulturedCD86MHC class IIbiologyMicrogliaHistocompatibility Antigens Class IIFOXP3Brainhemic and immune systemsForkhead Transcription FactorsCoculture TechniquesCell biologyInterleukin-10Mice Inbred C57BLmedicine.anatomical_structureCellular Microenvironmentbiology.proteinMicroglia

description

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+CD40dimCD86dimIL-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+CD40dimCD86dimIL-10+ microglia have regulatory properties potentially influencing local immune responses in the CNS.

yearjournalcountryeditionlanguage
2013-10-23Journal of immunology (Baltimore, Md. : 1950)
10.4049/jimmunol.1203331https://pubmed.ncbi.nlm.nih.gov/24146044