Cutting Edge: Human Regulatory T Cells Require IL-35 To Mediate Suppression and Infectious Tolerance | Zendy

Vandana Chaturvedi | Zendy; Lauren W. Collison | Zendy; Clifford S. Guy | Zendy; Creg J. Workman | Zendy; Dario A.A. Vignali | Zendy

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Cutting Edge: Human Regulatory T Cells Require IL-35 To Mediate Suppression and Infectious Tolerance

Author(s) -

Vandana Chaturvedi,

Lauren W. Collison,

Clifford S. Guy,

Creg J. Workman,

Dario A.A. Vignali

Publication year - 2011

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1100315

Subject(s) - treg cell , immune tolerance , downregulation and upregulation , immunology , immune system , microbiology and biotechnology , population , interleukin 10 , biology , il 2 receptor , medicine , t cell , gene , genetics , environmental health

Human regulatory T cells (T(reg)) are essential for the maintenance of immune tolerance. However, the mechanisms they use to mediate suppression remain controversial. Although IL-35 has been shown to play an important role in T(reg)-mediated suppression in mice, recent studies have questioned its relevance in human T(reg). In this study, we show that human T(reg) express and require IL-35 for maximal suppressive capacity. Substantial upregulation of EBI3 and IL12A, but not IL10 and TGFB, was observed in activated human T(reg) compared with conventional T cells (T(conv)). Contact-independent T(reg)-mediated suppression was IL-35 dependent and did not require IL-10 or TGF-β. Lastly, human T(reg)-mediated suppression led to the conversion of the suppressed T(conv) into iTr35 cells, an IL-35-induced T(reg) population, in an IL-35-dependent manner. Thus, IL-35 contributes to human T(reg)-mediated suppression, and its conversion of suppressed target T(conv) into IL-35-induced T(reg) may contribute to infectious tolerance.

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