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

Collison, Lauren W., Chaturvedi, Vandana, Henderson, Abigail L., Giacomin, Paul, Guy, Cliff, Bankoti, Jaishree, Finkelstein, David, Forbes, Karen, Workman, Creg J., Brown, Scott A., Rehg, Jerold E., Jones, Michael L., Ni, Hsiao-Tzu, Artis, David, Turk, Mary Jo, and Vignali, Dario A.A. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nature Immunology, 11 (12). pp. 1093-1101.

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Abstract

Regulatory T cells (T reg cells) have a critical role in the maintenance of immunological self-tolerance. Here we show that treatment of naive human or mouse T cells with IL-35 induced a regulatory population, which we call 'iTR35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 or transforming growth factor-β (TGF-β). We found that iTR35 cells did not express or require the transcription factor Foxp3, and were strongly suppressive and stable in vivo. T reg cells induced the generation of iTR35 cells in an IL-35- and IL-10-dependent manner in vitro and induced their generation in vivo under inflammatory conditions in intestines infected with Trichuris muris and within the tumor microenvironment (B16 melanoma and MC38 colorectal adenocarcinoma), where they contributed to the regulatory milieu. Thus, iTR35 cells constitute a key mediator of infectious tolerance and contribute to T reg cell–mediated tumor progression. Furthermore, iTR35 cells generated ex vivo might have therapeutic utility.

Item ID: 17711
Item Type: Article (Refereed Research - C1)
ISSN: 1529-2916
Date Deposited: 10 Oct 2011 03:54
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
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