Although previous studies with DGKα or ζ single-deficient mice have found that DGK activity inhibits T cell activation and proliferation as well as primary CD8 T cell-mediated immune response in vivo, our current study surprisingly reveal that simultaneous ablation of both DGKα and ζ severely impair CD8 T cell-mediated responses to bacterial infection, manifested by defective expansion of effector and formation of memory CD8 T cells after bacterial challenge and by impaired maintenance of CD8 memory T cells. Here, CD8A is linked to bacterial infectious disease.