Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA.
J Immunol. 2021 Oct 15;207(8):2086-2095. doi: 10.4049/jimmunol.2100405. Epub 2021 Sep 22.
CMV is a major infectious complication following solid organ transplantation. Reactivation of CMV leads to memory inflation, a process in which CD8 T cells expand over time. Memory inflation is associated with specific changes in T cell function, including increased oligoclonality, decreased cytokine production, and terminal differentiation. To address whether memory inflation during the first year after transplantation in human subjects alters T cell differentiation and function, we employed single-cell-matched TCRαβ and targeted gene expression sequencing. Expanded T cell clones exhibited a terminally differentiated, immunosenescent, and polyfunctional phenotype whereas rare clones were less differentiated. Clonal expansion occurring between pre- and 3 mo posttransplant was accompanied by enhancement of polyfunctionality. In contrast, polyfunctionality and differentiation state were largely maintained between 3 and 12 mo posttransplant. Highly expanded clones had a higher degree of polyfunctionality than rare clones. Thus, CMV-responsive CD8 T cells differentiated during the pre- to posttransplant period then maintained their differentiation state and functional capacity despite posttransplant clonal expansion.
巨细胞病毒（CMV）是实体器官移植后的主要感染并发症。CMV 的重新激活导致记忆膨胀，这是一个 CD8 T 细胞随时间扩张的过程。记忆膨胀与 T 细胞功能的特定变化相关，包括寡克隆性增加、细胞因子产生减少和终末分化。为了确定在人类受者移植后第一年的记忆膨胀是否改变 T 细胞分化和功能，我们采用了单细胞匹配的 TCRαβ 和靶向基因表达测序。扩增的 T 细胞克隆表现出终末分化、免疫衰老和多功能表型，而罕见的克隆分化程度较低。在移植前和移植后 3 个月之间发生的克隆扩增伴随着多功能性的增强。相比之下，在移植后 3 至 12 个月之间，多功能性和分化状态基本保持不变。高度扩增的克隆比罕见的克隆具有更高的多功能性。因此，CMV 反应性 CD8 T 细胞在移植前至移植后期间分化，然后尽管在移植后发生了克隆扩增，但仍保持其分化状态和功能能力。
