Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Renal Transplant Unit, Division of Internal Medicine, Academic Medical Centre, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Eur J Immunol. 2019 May;49(5):694-708. doi: 10.1002/eji.201847897. Epub 2019 Mar 25.
During acute viral infections in mice, IL-7Rα and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7Rα KLRG ) from the precursors of persisting memory cells (MPEC; IL-7Rα KLRG1 ). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in "steady state" in humans. In contrast to the T cells in the circulation, T cells derived from lymph nodes hardly contain any KLRG1-expressing cells. The four populations defined by IL-7Rα and KLRG1 differ markedly in transcription factor, granzyme and chemokine receptor expression. When studying renal transplant recipients experiencing a primary hCMV and EBV infection, we also found that after viral control, during latency, Ki-67-negative SLEC can be found in the peripheral blood in considerable numbers. Thus, combined analyses of IL-7Rα and KLRG1 expression on human herpes virus-specific CD8 T cells can be used to separate functionally distinct subsets in humans. As a noncycling IL-7Rα KLRG1 population is abundant in healthy humans, we conclude that this combination of markers not only defines short-lived effector cells during the acute response but also stable effector cells that are formed and remain present during latent herpes infections.
在小鼠的急性病毒感染中,IL-7Rα 和 KLRG1 共同用于区分短暂存活效应细胞(SLEC;IL-7Rα KLRG )和持续记忆细胞前体(MPEC;IL-7Rα KLRG1 )。我们在这里表明,这些标记物可用于在人类的急性阶段和“稳态”期间定义循环和淋巴结中的不同亚群。与循环中的 T 细胞不同,来自淋巴结的 T 细胞几乎不含任何表达 KLRG1 的细胞。通过 IL-7Rα 和 KLRG1 定义的四个群体在转录因子、颗粒酶和趋化因子受体表达方面差异显著。在研究经历原发性 hCMV 和 EBV 感染的肾移植受者时,我们还发现,在病毒控制后,潜伏期间,外周血中可以发现相当数量的 Ki-67 阴性 SLEC。因此,对人类疱疹病毒特异性 CD8 T 细胞上的 IL-7Rα 和 KLRG1 表达进行联合分析可用于分离人类中功能不同的亚群。由于非循环的 IL-7Rα KLRG1 群体在健康人中大量存在,我们得出结论,这种标记物的组合不仅在急性反应期间定义了短暂存活的效应细胞,而且还定义了在潜伏性疱疹感染期间形成并持续存在的稳定效应细胞。