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Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

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Figshare2016-10-27 更新2026-04-29 收录
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CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential.

CD11c(α整合素)是经典用于鉴定髓系树突状细胞的整合素亚类。尽管目前关于人类T细胞表面CD11c的表达情况尚缺乏充分研究,但小鼠模型研究已证实CD11c的表达与功能特征明确的T细胞亚群存在关联。在生殖道感染的研究背景下,本课题组此前已观察到,小鼠与女性受试者的循环T细胞中CD11c的表达水平显著升高。对来自未致敏小鼠的CD11c阳性活化效应T细胞进行的基因芯片分析显示,其富集了与自然杀伤(NK)细胞相关的基因。本研究通过流式细胞术分析小鼠CD11c阳性T细胞后发现,这群细胞表达与非常规T细胞亚群相关的标志物,包括γδ T细胞与不变型自然杀伤T(iNKT)细胞。但在女性受试者中,血液与宫颈组织的CD11c阳性组分中仅富集了γδ T细胞与CD8阳性T细胞。此类CD11c阳性细胞处于高度活化状态,且相较于CD11c阴性T细胞,其分泌干扰素(IFN)-γ的能力显著更强。此外,女性受试者体内的循环CD11c阳性T细胞高表达多种黏附分子,提示这群细胞具备极强的组织归巢潜能。综上,本研究数据表明,在细菌感染过程中,CD11c的表达可用于区分一类具备先天功能特性与黏膜归巢潜能的循环T细胞亚群。

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2016-10-27
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