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

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Wang, Shaoying | Prieux, Margaux | de Bernard, Simon | Dubois, Maxence | Laubreton, Daphne | Djebali, Sophia | Zala, Manon | Arpin, Christophe | Genestier, Laurent | Leverrier, Yann | Gandrillon, Olivier | Crauste, Fabien | Jiang, Wenzheng | Marvel, Jacqueline

Edité par CCSD ; Elsevier -

International audience. 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.

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