IL-35-mediated induction of a potent regulatory T cell population.

Regulatory T cells (Tregs) play a critical role in the maintenance of immunological self-tolerance. Nave human or murine T cell treatment with the inhibitory cytokine IL35 induces a regulatory population, termed iTR35, that mediates suppression via IL35, but not IL10 or TGF, neither express nor require Foxp3, are strongly suppressive in five in vivo models, and exhibit in vivo stability. Treg-mediated suppression induces iTR35 generation in an IL35- and IL10-dependent manner in vitro, and in inflammatory conditions in vivo in Trichuris-infected intestines and within the tumor microenvironment, where they appear to contribute to the regulatory milieu. iTR35 may constitute a key mediator of infectious tolerance and may contribute to Treg-mediated tumor progression, and ex vivo-generated iTR35 may possess therapeutic utility.

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