Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cells

Magali Terme, Nathalie Chaput, Behazine Combadiere, Ma Averil, Toshiaki Ohteki, Laurence Zitvogel

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    82 Citations (Scopus)

    Abstract

    The CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the control of peripheral tolerance by directly inhibiting conventional T cell proliferative and effector functions. However, the mechanisms by which Treg regulate the homeostasis of lymph nodes remain unclear. In this study, we show in a mouse model that Treg control two major checkpoints dictated by the interaction between self-reactive CD4+ T cells and resident dendritic cell (DC) in secondary lymphoid organs. First, Treg inhibit the production of CCR5 ligands, limiting the CCR5-dependent recruitment of DC in the lymph nodes. Second, Treg prevent the DC exposure of IL-15Rα, markedly interfering in the DC-mediated NK cell proliferation in vivo. Therefore, the DC/T cell autoreactivity leading to NK cell triggering could potentially be controlled by the coinhibition of both IL-15Rα and CCR5 in autoimmune disorders in which NK cells play a deleterious role.

    Original languageEnglish
    Pages (from-to)4679-4686
    Number of pages8
    JournalJournal of Immunology
    Volume180
    Issue number7
    DOIs
    Publication statusPublished - 1 Apr 2008

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