Translation inhibitor PDCD4 promotes CD8+ T cell proliferation during antiviral response

Abstract CD8+ T cell clonal expansion is critical for controlling intracellular infections and tumors. Thus, unravelling the mechanisms that regulate proliferation are imperative to improve vaccine design immunotherapy. However, molecular govern still not fully understood. PDCD4 (Programmed death 4) was shown inhibit translation by sequestering mRNA helicase eIF4A, which leads inhibition of genes involved in proliferation. Despite well-characterized anti-proliferative role PDCD4, our studies suggest promotes during phase acute LCMV infection. We find over-expressed Ag-specific cells have higher rate increased number compared control cells. Consistent with over-expression results, knocking-down undergo less proliferation, resulting reduced controls. Interestingly, contrary paradigm generates more short-lived effector cells, mediated does skew differentiation memory precursor This also confirmed a constitutively active form resists degradation endogenous ubiquitin pathway. In conclusion, work has identified novel pro-proliferative response. Supported grants from NIH (R01 AI139675)