Suppression of caspase 8 activity by a coronin 1-PI3Kδ pathway promotes T cell survival independently of TCR and IL-7 signaling

The control of T cell survival is crucial for defense against infectious pathogens or emerging cancers. Although the survival of peripheral naive T cells has been proposed to be controlled by interleukin-7 (IL-7) signaling and T cell receptor (TCR) activation by peptide-loaded major histocompatibility complexes (pMHC), the essential roles for these pathways in thymic output and T cell proliferation have complicated the analysis of their contributions to T cell survival. Here, we showed that the WD repeat-containing protein coronin 1, which is dispensable for thymic selection and output, promoted naive T cell survival in the periphery in a manner that was independent of TCR and IL-7 signaling. Coronin 1 was required for the maintenance of the basal activity of phosphoinositide 3-kinase delta (PI3K delta), thereby suppressing caspase 8-mediated apoptosis. These results therefore reveal a coronin 1-dependent PI3K delta pathway that is independent of pMHC:TCR and IL-7 signaling and essential for peripheral T cell survival.