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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.


Suzanne P M Welten, Alexander Yermanos, Nicolas S Baumann, Franziska Wagen, Nathalie Oetiker, Ioana Sandu, Alessandro Pedrioli, Jennifer D Oduro, Sai T Reddy, Luka Cicin-Sain, Werner Held, Annette Oxenius. Tcf1+ cells are required to maintain the inflationary T cell pool upon MCMV infection. Nature communications. 2020 May 08;11(1):2295

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PMID: 32385253

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