A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1
A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1
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DOI：
10.1172/jci57990
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发表时间：
2012-01-01
影响因子：
15.9
通讯作者：
Koenderman, Leo
中科院分区：
文献类型：
--
作者：
Pillay, Janesh;Kamp, Vera M.;Koenderman, Leo
免疫应答的抑制对于限制炎症期间对宿主组织的损伤是必要的，但它在特异性免疫应答中可能是有害的，例如脓毒症和抗肿瘤免疫。最近，未成熟骨髓细胞被认为与癌症、传染病、骨髓移植和自身免疫性疾病小鼠模型中免疫反应的抑制有关。在这里，我们报告了一个成熟的人中性粒细胞亚群（CD 11 c（亮）/CD 62 L（暗）/CD 11b（亮）/CD（16 bright））的鉴定，我们认为这是一个独特的骨髓细胞循环群体，能够抑制人T细胞增殖。这些细胞在人体内由内毒素攻击或严重损伤诱导的急性全身炎症期间观察到。中性粒细胞局部释放过氧化氢进入中性粒细胞和T细胞之间的免疫突触，介导了T细胞增殖的抑制，并需要中性粒细胞表达整合素Mac-1（α M β 2）。我们的数据表明，T细胞功能的抑制可以通过人类中性粒细胞的一个子集，可以全身诱导急性炎症反应来完成。中性粒细胞Mac-1和ROS在这一过程中的关键作用的鉴定为调节人类免疫应答提供了潜在的靶点。
Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11c(bright)/CD62L(dim)/CD11b(brigh)/CD(16bright)) as what we believe to be a unique circulating population of myeloid cells, capable of suppressing human T cell proliferation. These cells were observed in humans in vivo during acute systemic inflammation induced by endotoxin challenge or by severe injury. Local release of hydrogen peroxide from the neutrophils into the immunological synapse between the neutrophils and T cells mediated the suppression of T cell proliferation and required neutrophil expression of the integrin Mac-1 (alpha M beta 2). Our data demonstrate that suppression of T cell function can be accomplished by a subset of human neutrophils that can be systemically induced in response to acute inflammation. Identification of the pivotal role of neutrophil Mac-1 and ROS in this process provides a potential target for modulating immune responses in humans.