Follicular CD8 + T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8 + T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8 + T cells. Transcriptional analysis of LN CD8 + T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5 + fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

中文翻译：

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溶细胞性 CD8 + T 细胞浸润生发中心以限制自发控制淋巴结中正在进行的 HIV 复制

滤泡CD8+T 细胞 (fCD8) 在淋巴结 (LN) 生发中心介导针对嗜淋巴细胞感染和癌症的监测，但这些细胞介导免疫控制的确切机制仍未完全解决。为了解决这个问题，我们研究了 LN 驻留病毒特异性 CD8 的功能、克隆型区室化、空间定位、表型特征和转录谱+无需药物即可控制 HIV 的人体内的 T 细胞。抗原诱导的增殖和细胞溶解潜能始终将自发控制者与非控制者区分开来。T 细胞受体分析显示外周和 LN 驻留 HIV 特异性 CD8 之间完全克隆型重叠+T 细胞。LN CD8 的转录分析+T 细胞揭示了炎症趋化性和抗原诱导的效应子功能的基因特征。在 HIV 控制者中，细胞毒性效应因子穿孔素和颗粒酶 B 在病毒特异性 CXCR5 中升高+fCD8s 靠近生发中心内的 HIV RNA 病灶。这些结果提供的证据与 fCD8s 的炎症募集、抗原特异性增殖和细胞毒性支持的嗜淋巴细胞感染控制一致。