Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nat Immunol. 2010 Dec;11(12):1093-101. doi: 10.1038/ni.1952. Epub 2010 Oct 17.
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-β (TGF-β). 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.
调节性 T 细胞（Treg 细胞）在维持免疫耐受中具有关键作用。在这里，我们表明，IL-35 处理幼稚的人或鼠 T 细胞可诱导调节性群体，我们称之为“iT(R)35 细胞”，其通过 IL-35 而不是通过抑制性细胞因子 IL-10 或转化生长因子-β（TGF-β）介导抑制。我们发现，iT(R)35 细胞不表达或需要转录因子 Foxp3，并且在体内具有强烈的抑制作用和稳定性。Treg 细胞以 IL-35 和 IL-10 依赖的方式在体外诱导 iT(R)35 细胞的产生，并在感染旋毛虫的肠道和肿瘤微环境（B16 黑色素瘤和 MC38 结直肠腺癌）的炎症条件下诱导其在体内产生，在那里它们有助于调节环境。因此，iT(R)35 细胞构成了感染性耐受的关键介质，并有助于 Treg 细胞介导的肿瘤进展。此外，体外生成的 iT(R)35 细胞可能具有治疗用途。
