CTLA-4 modulates the differentiation of inducible foxp3+treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis

Johan Verhagen*, Leona Gabryšová, Ella R. Shepard, David C. Wraith

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)

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.

Original languageEnglish
Article numbere108023
JournalPLoS ONE
Volume9
Issue number9
DOIs
Publication statusPublished - 19 Sep 2014

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