Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ 85724-5073, USA.
J Leukoc Biol. 2012 Nov;92(5):987-97. doi: 10.1189/jlb.0911465. Epub 2012 Aug 13.
MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined. Previous reports have suggested that MDSC may contribute to Treg induction in cancer. Herein, we provide evidence that tumor-induced gr-MDSCs, endowed with the potential of suppressing conventional T Lc, surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs. Furthermore, gr-MDSCs impede the proliferation of nTregs without, however, affecting FoxP3 expression. Suppression of iTreg differentiation from naïve CD4(+) cells by gr-MDSC occurs early in the polarization process, requires inhibition of early T cell activation, and depends on ROS and IDO but does not require arginase 1, iNOS, NO, cystine/cysteine depletion, PD-1 and PD-L1 signaling, or COX-2. These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs.
髓系来源抑制细胞（MDSCs）和调节性 T 细胞（Tregs）在肿瘤免疫逃逸中发挥重要作用。肿瘤促进这些抑制性细胞扩增和/或功能的机制以及 MDSC 和 Treg 之间的串扰仍不完全明确。先前的报告表明，MDSC 可能有助于癌症中 Treg 的诱导。在此，我们提供的证据表明，肿瘤诱导的粒细胞 MDSC 具有抑制常规 T 细胞的潜力，令人惊讶的是，它损害了 TGF-β1 介导的 CD4+CD25+FoxP3+iTreg 的产生。此外，粒细胞 MDSC 抑制 nTreg 的增殖，但不影响 FoxP3 的表达。粒细胞 MDSC 从幼稚 CD4+细胞中抑制 iTreg 分化发生在极化过程的早期，需要抑制早期 T 细胞激活，并依赖于 ROS 和 IDO，但不依赖于精氨酸酶 1、NOS、NO、半胱氨酸/胱氨酸耗竭、PD-1 和 PD-L1 信号或 COX-2。这些发现表明，来自结核宿主的粒细胞 MDSC 具有出乎意料的限制免疫抑制性 Treg 的能力。
