Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany.
J Immunol. 2010 Jul 1;185(1):203-10. doi: 10.4049/jimmunol.0903573. Epub 2010 Jun 4.
Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that negatively regulate the immune response during tumor progression, inflammation, and infection. In this study, through gene-expression analysis, we have identified a new marker, CD49d, which is expressed exclusively on CD11b(+)Gr-1(dull/int.) MDSCs. We have characterized two subpopulations of MDSCs based on CD49d expression in two different settings, a mouse model of inflammatory bowel disease and tumor-bearing mice. The CD49d(+) subset of MDSCs was mainly monocytic and strongly suppressed Ag-specific T cell proliferation in an NO-dependent mechanism similar to Gr-1(dull/int.) MDSCs. Alternatively, CD49d(-) cells were granulocytic and poorly inhibited T cell proliferation compared with CD11b(+)Gr-1(high) cells. Both mouse models showed preferential expansion of the granulocytic CD49d(-) subset. We suggest that CD49d can be used as an alternative marker for Gr-1 to differentiate between the subpopulations of MDSCs together with CD11b, which will ultimately help in understanding the mechanisms of immune suppression by MDSCs.
髓系来源的抑制细胞（MDSCs）是一种异质性细胞群体，在肿瘤进展、炎症和感染过程中负向调节免疫反应。在这项研究中，我们通过基因表达分析，鉴定了一个新的标志物 CD49d，它仅在 CD11b(+)Gr-1(dull/int.) MDSCs 上表达。我们根据 CD49d 的表达，在两种不同的情况下，即炎症性肠病小鼠模型和荷瘤小鼠中，对 MDSCs 的两个亚群进行了特征描述。CD49d(+) MDSC 亚群主要为单核细胞，以类似于 Gr-1(dull/int.) MDSCs 的 NO 依赖性机制强烈抑制 Ag 特异性 T 细胞增殖。相比之下，CD49d(-)细胞与 CD11b(+)Gr-1(high)细胞相比，对 T 细胞增殖的抑制作用较差。两种小鼠模型均显示出粒细胞性 CD49d(-)亚群的优先扩增。我们认为，CD49d 可以与 CD11b 一起作为 Gr-1 的替代标志物，用于区分 MDSCs 的亚群，这将有助于最终理解 MDSCs 免疫抑制的机制。
