RETRACTED: Cutting Edge: Human Regulatory T Cells Require IL-35 To Mediate Suppression and Infectious Tolerance (Retracted article. See vol. 191, pg. 2018, 2013)

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-beta. 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. The Journal of Immunology, 2011, 186: 6661-6666.