Gladstone Institute of Virology, San Francisco, CA.
Department of Urology, University of California San Francisco, San Francisco, CA.
J Immunol. 2022 Apr 1;208(7):1790-1801. doi: 10.4049/jimmunol.2101102. Epub 2022 Mar 16.
T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but they differ in the kinds of foreign Ags they need to tolerate. How these different environments influence the properties of their T cells is poorly understood, but important for understanding women's health. We recruited antiretroviral therapy-suppressed women living with HIV who donated, within one visit, blood and tissue samples from the ileum, colon, rectosigmoid, endometrium, endocervix, and ectocervix. With these samples, we conducted 36-parameter cytometry by time of flight phenotyping of T cells. Although gut and FRT T cells shared features discriminating them from their blood counterparts, they also harbored features distinguishing them from one another. These included increased proportions of CD69 T resident memory cells of the T effector memory phenotype, as well as preferential coexpression of CD69 and CD103, on the gut-derived cells. In contrast, CD69CD103 T resident memory CD8 T cells from FRT, but not those from gut, preferentially expressed PD1. We further determined that a recently described population of CXCR4 T inflammatory mucosal cells differentially expressed multiple other chemokine receptors relative to their blood counterparts. Our findings suggest that T cells resident in different tolerogenic mucosal sites take on distinct properties.
驻留在黏膜组织中的 T 细胞在维持体内平衡和抵御微生物病原体方面发挥着重要作用。肠道和女性生殖道(FRT)都是耐受环境,但它们需要耐受的外来抗原种类不同。这些不同的环境如何影响它们的 T 细胞特性尚不清楚,但对于了解女性健康很重要。我们招募了接受抗逆转录病毒治疗抑制的 HIV 感染者,她们在一次就诊中捐献了回肠、结肠、直肠乙状结肠、子宫内膜、宫颈内口和宫颈外口的血液和组织样本。我们使用这些样本对 T 细胞进行了 36 个参数的时间飞行流式细胞术表型分析。尽管肠道和 FRT 的 T 细胞与血液中的 T 细胞具有共同的特征,但它们也具有彼此区分的特征。这些特征包括增加了 CD69 T 效应记忆表型的驻留记忆细胞的比例,以及肠道衍生细胞上 CD69 和 CD103 的优先共表达。相比之下,FRT 而不是肠道来源的 CD69CD103 T 驻留记忆 CD8 T 细胞优先表达 PD1。我们进一步确定,最近描述的一种 CXCR4 T 炎症性黏膜细胞群体相对于其血液对应物,表达多种其他趋化因子受体。我们的研究结果表明,驻留在不同耐受黏膜部位的 T 细胞具有不同的特性。