Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
Department of Biosystems and Engineering, ETH Zürich, Mattenstrasse 26, 4058, Basel, Switzerland.
Nat Commun. 2020 May 8;11(1):2295. doi: 10.1038/s41467-020-16219-3.
Cytomegalovirus-based vaccine vectors offer interesting opportunities for T cell-based vaccination purposes as CMV infection induces large numbers of functional effector-like cells that accumulate in peripheral tissues, a process termed memory inflation. Maintenance of high numbers of peripheral CD8 T cells requires continuous replenishment of the inflationary T cell pool. Here, we show that the inflationary T cell population contains a small subset of cells expressing the transcription factor Tcf1. These Tcf1 cells resemble central memory T cells and are proliferation competent. Upon sensing viral reactivation events, Tcf1 cells feed into the pool of peripheral Tcf1 cells and depletion of Tcf1 cells hampers memory inflation. TCR repertoires of Tcf1 and Tcf1 populations largely overlap, with the Tcf1 population showing higher clonal diversity. These data show that Tcf1 cells are necessary for sustaining the inflationary T cell response, and upholding this subset is likely critical for the success of CMV-based vaccination approaches.
巨细胞病毒（Cytomegalovirus，CMV）为基础的疫苗载体为 T 细胞疫苗接种提供了有趣的机会，因为 CMV 感染会诱导大量功能性效应样细胞在周围组织中积累，这一过程被称为记忆膨胀。维持大量外周血 CD8 T 细胞需要不断补充膨胀的 T 细胞池。在这里，我们发现膨胀的 T 细胞群中包含一小部分表达转录因子 Tcf1 的细胞。这些 Tcf1 细胞类似于中央记忆 T 细胞，并且具有增殖能力。当感知到病毒再激活事件时，Tcf1 细胞会进入外周 Tcf1 细胞池，而 Tcf1 细胞的耗竭会阻碍记忆膨胀。Tcf1 和 Tcf1 群体的 TCR 库大部分重叠，Tcf1 群体显示出更高的克隆多样性。这些数据表明 Tcf1 细胞对于维持膨胀的 T 细胞反应是必要的，维持这个亚群对于基于 CMV 的疫苗接种方法的成功可能是至关重要的。
