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

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.