Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection.
Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection.
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大多数人类单纯疱疹病毒2型（HSV-2）的再激活是亚临床的，与病毒的快速扩增和遏制有关。先前的研究表明，CD 8 + T细胞在病变清除后的较长时间内持续存在于生殖器皮肤和粘膜的真皮-表皮交界处（DEJ），这是神经元释放再活化病毒的门户。这种持久性CD 8 + T细胞群体的表型和功能仍然未知。在这里，使用细胞类型特异性激光捕获显微切割，转录谱和T细胞受体β（TCRβ）基因分型的连续生殖器皮肤活检，我们表明CD 8 αα+ T细胞是主要的居民群体DEJ CD 8 + T细胞，坚持在网站上的HSV-2再激活。位于DEJ的CD 8 αα+ T细胞缺乏淋巴细胞流出和再循环所需的趋化因子受体表达，表达T细胞活化和抗病毒活性的基因特征，并在临床和病毒学静止期产生溶细胞颗粒。TCRβ链库的测序显示，DEJ CD 8 αα+ T细胞是寡克隆的，具有不同的TCR VB基因使用，这与MAIT和NKT细胞通常描述的不同。在两年半的时间内，多个复发事件之间的优势克隆型重叠。快速无症状HSV-2遏制的发生也与高CD 8效应细胞与靶细胞比率和CD 8 αα+ T细胞的局灶性富集相关。这些研究表明，DEJ CD 8 αα+ T细胞是组织驻留细胞，似乎在免疫监视和人类外周组织中HSV-2再活化的初始遏制中发挥重要作用。诱导CD 8 αα+ T细胞可能是开发有效的皮肤和粘膜感染疫苗的关键组成部分。
Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown CD8+ T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ), the portal of neuronal release of reactivating virus, for prolonged time periods after lesions are cleared. The phenotype and function of this persistent CD8+ T-cell population remain unknown. Here, using cell type-specific laser capture microdissection, transcriptional profiling and T-cell receptor beta (TCRβ) genotyping on sequential genital skin biopsies, we show CD8αα+ T cells are the dominant resident population of DEJ CD8+ T cells that persist at the site of prior HSV-2 reactivation. CD8αα+ T cells located at the DEJ lack chemokine receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCRβ chain repertoire revealed that the DEJ CD8αα+ T cells are oligoclonal with diverse usage of TCR VB genes, which differ from those commonly described for MAIT and NKT cells. Dominant clonotypes overlapped among multiple recurrence episodes over a period of two and a half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8αα+ T cells. These studies indicate DEJ CD8αα+ T cells are tissue resident cells that appear to play a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8αα+ T cells might be a critical component for developing effective vaccines against skin and mucosal infections.
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