Uncovering the role of STAT5 in CD8+ T cell fate

Abstract Long-term protection against infection and disease requires long-lived memory CD8+ T cells. The development of these cells a differentiation process influenced by cytokines – such as IL-2, IL-7, IL-15 that are known to mediate the balance between effector populations. Interestingly, act through common activation STAT5, however, mechanisms which STAT5 dictates cell fate is poorly understood. To elucidate how affects differentiation, we have developed strategy activate endogenous in absence cytokine. We compared cultured cytokine promote cells, those where was directly activated. found direct resulted decreased IFNγ production comparison IL-2 treatment. This observation led us evaluate expression transcription factors proteins related effector, memory, exhausted states. Our results demonstrate experience higher levels TCF1 lower granzyme B IL-2. gain an understanding phenotypic changes state, performed bulk RNA sequencing assess global gene expression. indicate when causes increased genes phenotype corresponding decrease or phenotype. findings suggest critical memory-like could be harnessed for therapeutic benefit cell-based treatments. Supported grants from V Foundation Concern