Rastad Jessica L, Green William R
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States.
Virology. 2016 Dec;499:9-22. doi: 10.1016/j.virol.2016.08.031. Epub 2016 Sep 12.
Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression.
在LP - BM5逆转录病毒感染期间，单核细胞来源的髓系抑制细胞（M - MDSCs）数量增加，并且它们不仅能够抑制T细胞反应，还能抑制B细胞反应。除了之前所证明的依赖诱导型一氧化氮合酶（iNOS）和VISTA的M - MDSC机制外，在本文中，我们详细阐述了M - MDSCs如何利用可溶性介质，包括活性氧和氮物种超氧化物、过氧亚硝酸盐和一氧化氮，以及转化生长因子-β（TGF - β），以一种主要非接触依赖的方式抑制B细胞。抑制作用与半胱氨酸耗竭和过氧化氢生成无关。当在双敲除小鼠中消除两种主要抑制机制（iNOS和VISTA）时，来自LP - BM5感染小鼠的M - MDSCs能够利用其他可溶性机制进行补偿，以维持对B细胞的抑制。产生白细胞介素-10的调节性B细胞亚群是M - MDSC介导的抑制作用的靶标之一。
