Defective cytoskeletal dynamics underlies the essential role of MRTF-SRF in IL-2 delivery to CD8+ T cells during infectious challenge
Paracrine IL-2 signalling underpins late primary CD8+ T cell expansion and differentiation that allow protection against viral infections, yet the requirements for effective delivery of IL-2 to recipient cells remain poorly understood. We show that the SRF transcription factor, a master regulator of cytoskeletal dynamics, is essential for the response to L. monocytogenes infection. SRF acts cell-autonomously with its actin-regulated MRTF cofactors Mrtfa and Mrtfb to sustain CD8+ effector T cell expansion and persistence of memory cells. MRTF-SRF activity is not required for initial TCR-mediated CD8+ T cell proliferation, but is necessary for subsequent IL-2 dependent expansion. Following TCR activation in vitro, Mrtfab-null CD8+ T cells produce IL-2 normally, but exhibit defective paracrine IL-2 signalling. Cluster formation by activated Mrtfab-null CD8+ T cells is impaired: clusters are smaller and less dense, have substantially reduced F-actin content, retain less IL-2, and exhibit defective cytoskeletal gene expression. Activated Mrtfab-null CD8+ T cells also exhibit defective homotypic clustering in vivo. The requirement for MRTF-SRF signalling for CD8+ T cell proliferation during infection thus reflects its involvement in cytoskeletal dynamics.