In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response

Shimpei Kasagi, Pin Zhang, Li Che, Brittany Abbatiello, Takashi Maruyama, Hiroko Nakatsukasa, Peter Zanvit, Wenwen Jin, Joanne E. Konkel, Wan Jun Chen

    Research output: Contribution to journalArticlepeer-review

    49 Citations (Scopus)

    Abstract

    Harnessing regulatory T (Treg) cells is a promising approach for treating autoimmune disease. However, inducing antigen-specific Treg cells that target inflammatory immune cells without compromising beneficial immune responses has remained an unmet challenge. We developed a pathway to generate autoantigen-specific Treg cells in vivo, which showed therapeutic effects on experimental autoimmune encephalomyelitis and nonobese diabetes in mice. Specifically, we induced apoptosis of immune cells by systemic sublethal irradiation or depleted B and CD8+ T cells with specific antibodies and then administered autoantigenic peptides in mice with established autoimmune diseases. We demonstrated mechanistically that apoptotic cells triggered professional phagocytes to produce transforming growth factor-β, under which the autoantigenic peptides directed naïve CD4+ T cells to differentiate into Foxp3+ Treg cells instead of into T effector cells in vivo. These antigen-specific Treg cells specifically ameliorated autoimmunity without compromising immune responses to bacterial antigen. We have thus successfully generated antigen-specific T reg cells with therapeutic activity toward autoimmunity. The findings may lead to the development of antigen-specific Treg cell-mediated immunotherapy for multiple sclerosis and type 1 diabetes and also other autoimmune diseases.

    Original languageEnglish
    Article number241ra78
    JournalScience Translational Medicine
    Volume6
    Issue number241
    DOIs
    Publication statusPublished - 2014 Jun 18

    ASJC Scopus subject areas

    • Medicine(all)

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