title: Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis.
abstract: In vitro induced Foxp3+ T regulatory (iTreg) cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP)-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Johan
authors.initials: J
authors.lastname: Verhagen
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Leona
authors.initials: L
authors.lastname: Gabryšová
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Ella R
authors.initials: ER
authors.lastname: Shepard
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Wraith
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D004679:Encephalomyelitis / Q000276:immunology / Q000473:pathology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10