Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.
Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.
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人类女性生殖道中单纯疱疹病毒2型（HSV-2）反应性粘膜T细胞的富集。
DOI：
10.1038/mi.2016.118
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发表时间：
2017-09
影响因子：
8
通讯作者：
Koelle DM
中科院分区：
文献类型：
--
作者：
Posavad CM;Zhao L;Dong L;Jin L;Stevens CE;Magaret AS;Johnston C;Wald A;Zhu J;Corey L;Koelle DM
局部粘膜细胞免疫在提供抗HSV-2的保护中至关重要。为了表征和定量HSV-2反应性粘膜T细胞，从17名HSV-2感染妇女的宫颈内细胞刷和活检标本中分离淋巴细胞，并离体检查与成熟和组织驻留相关的标志物的表达以及对HSV-2的功能性T细胞应答。与其循环对应物相比，宫颈来源的CD 4+和CD 8 + T细胞主要是效应记忆T细胞（CCR 7-/CD 45 RA-），大多数表达CD 69，这是组织驻留的标志物。CD 103的共表达，组织驻留的另一个标志物，是最高的宫颈来源的CD 8 + T细胞。在宫颈样本中检测到功能性HSV-2反应性CD 4+和CD 8 + T细胞应答，并且共表达CD 103的中位数为17%。HSV-2反应性CD 4 + T细胞共表达IL-2，并且与血液相比在宫颈中显著富集。这第一次直接离体文件的局部富集HSV-2反应性T细胞在人类女性生殖器粘膜是一致的抗原特异性组织驻留记忆T细胞的存在。这些T细胞的离体分析可能揭示HSV-2局部控制的组织特异性机制，以帮助开发将保护性T细胞靶向HSV-2感染部位的疫苗策略。
Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantitate HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T cell responses to HSV-2. Compared to their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7−/CD45RA−) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T cells responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2 reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared to blood. This first direct ex vivo documentation of local enrichment of HSV-2 reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.