Recent thymic emigrants preferentially undergo memory inflation after persistent infection

Cytomegalovirus (CMV) leads to a unique phenomenon known as ‘memory inflation,’ where antigen-specific memory CD8 + T cells continue to accumulate in the peripheral tissues during the latent stage of infection. However, it is still not clear how the inflating pool of memory CD8 + T cells is generated and maintained. In this study, we used murine cytomegalovirus (MCMV) as a model of persistent infection and fate-mapping mice to determine the dynamics of CD8 + T cell recruitment into the memory pool. We found that neonatal exposure to CMV leads to an expansion of newly produced CD8 + T cells called recent thymic emigrants, or RTEs, which are maintained in the long-lived memory compartment. In contrast, CD8 + T cells produced after the acute phase of infection contribute minimally to memory inflation. We also observed notable phenotypic differences between the RTEs and mature CD8 + T cells that were recruited into the memory inflation response. Whereas the RTEs present at the time of infection gave rise to more effector memory cells, the mature CD8 + T cells were biased towards becoming central memory cells. Importantly, the preferential recruitment of RTEs into the effector memory pool also occurs during adult exposure to CMV. Collectively, these data demonstrate that persistent infection expands the RTE population, and timing of infection dictates whether neonatal or adult RTEs are ‘locked in’ to the memory pool.