Exogenous IL-2 delays memory precursors generation and is essential for enhancing memory cells effector functions

To investigate the impact of paracrine IL -2 signals on memory precursor (MP) cell differentiation, we activated CD8 T cell in vitro in the presence or absence of exogenous IL -2 (ex -IL -2). We assessed memory differentiation by transferring these cells into virus -infected mice. Both conditions generated CD8 T cells that participate in the ongoing response and gave rise to similar memory cells. Nevertheless, when transferred into a naive host, T cells activated with ex -IL -2 generated a higher frequency of memory cells displaying increased functional memory traits. Single -cell RNA-seq analysis indicated that without ex -IL -2, cells rapidly acquire an MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a functional assay. Overall, ex -IL -2 delays the transition into MP cells, allowing the acquisition of effector functions that become imprinted in their progeny. These findings may help to optimize the generation of therapeutic T cells.