CD49d Is a New Marker for Distinct Myeloid-Derived Suppressor Cell Subpopulations in Mice

CD49d Is a New Marker for Distinct Myeloid-Derived Suppressor Cell Subpopulations in Mice
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DOI:
10.4049/jimmunol.0903573
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发表时间:
2010-07-01
影响因子:
4.4
通讯作者:
Greten, Tim F.
Greten, Tim F.
中科院分区:
医学2区
文献类型:
--
作者:
Haile, Lydia A.;Gamrekelashvili, Jaba;Greten, Tim F.

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髓系来源的抑制细胞(MDSCs)是一种异质性细胞群,在肿瘤进展、炎症和感染过程中负向调节免疫反应。在本研究中,通过基因表达分析,我们发现了一个新的标记CD49d,它只在CD11b(+)Gr-1(dull/int)上表达。MDSCs。我们根据CD49d的表达在两种不同的环境中表征了两种MDSCs亚群,一种是炎症性肠病的小鼠模型,另一种是荷瘤小鼠。MDSCs的CD49d(+)亚群主要是单核细胞,强烈抑制抗原特异性T细胞的增殖,其机制类似于Gr-1(Dull/int)。MDSCs。与CD11b(+)Gr-1(高)细胞相比,CD49d(-)细胞为粒细胞,对T细胞增殖的抑制作用较弱。两种小鼠模型均显示粒细胞CD49d(-)亚群优先扩增。我们建议CD49d可作为GR-1的替代标记,与CD11b一起区分MDSCs亚群,最终有助于了解MDSCs的免疫抑制机制。《免疫学杂志》,2010,185:203-210。
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. The Journal of Immunology, 2010, 185: 203-210.