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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.

Tcf1+ cells are required to maintain the inflationary T cell pool upon MCMV infection