title: Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance.
abstract: 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.
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Chaturvedi
authors.forename: Lauren W
authors.initials: LW
authors.lastname: Collison
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Guy
authors.forename: Creg J
authors.initials: CJ
authors.lastname: Workman
authors.forename: Dario A A
authors.initials: DA
authors.lastname: Vignali
mesh_terms: D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10; D053765:Interleukin-12 Subunit p35; D007378:Interleukins / Q000276:immunology*; D015778:Minor Histocompatibility Antigens; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta
chemical_list: C097732:EBI3 protein, human; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D016212:Transforming Growth Factor beta; C532417:interleukin-35, human; D016753:Interleukin-10