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

被引:682
作者
Collison, Lauren W. [1 ]
Chaturvedi, Vandana [1 ]
Henderson, Abigail L. [1 ]
Giacomin, Paul R. [2 ,3 ]
Guy, Cliff [1 ]
Bankoti, Jaishree [1 ]
Finkelstein, David [4 ]
Forbes, Karen [1 ]
Workman, Creg J. [1 ]
Brown, Scott A. [1 ]
Rehg, Jerold E. [5 ]
Jones, Michael L. [6 ]
Ni, Hsiao-Tzu [7 ]
Artis, David [2 ,3 ]
Turk, Mary Jo [8 ]
Vignali, Dario A. A. [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA
[4] St Jude Childrens Res Hosp, Dept Bioinformat, Memphis, TN 38105 USA
[5] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
[6] Shenandoah Biotechnol, Monroe, OH USA
[7] R&D Syst, Dept Antibody Applicat, Minneapolis, MN USA
[8] Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH USA
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
INFECTIOUS TOLERANCE; TUMOR-IMMUNITY; CUTTING EDGE; ACTIVATION; ENCEPHALOMYELITIS; CONTRIBUTES; EXPRESSION; GENERATION; RESPONSES; EFFECTOR;
D O I
10.1038/ni.1952
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 'iT(R)35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 or transforming growth factor-beta (TGF-beta). We found that iT(R)35 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 iT(R)35 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, iT(R)35 cells constitute a key mediator of infectious tolerance and contribute to T-reg cell-mediated tumor progression. Furthermore, iT(R)35 cells generated ex vivo might have therapeutic utility.
引用
收藏
页码:1093 / U97
页数:11
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