Exogenous IL-2 delays the generation of memory precursor cells and is essential for the generation of memory cells with increased 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 the memory differentiation of activated T cells by transfer into virus-infected mice. Both conditions generated CD8 T cells that participate in the ongoing immune response and gave rise to similar memory cells. Conversely, 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 a MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a killing 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. Overall design: To investigate the transcriptional changes that IL-2 could mediate over the course of in vitro activation, we activated F5 CD8 T cells for 3, 4 or 5 days in the absence or presence of ex-IL-2. Naive cells (=day 0) were used as a control (7 different conditions). These cells were then isolated by Fluorescence-activated cell sorting (FACS) and analyzed using single-cell RNA-seq