AbstractBacterial phagocytosis and antigen cross-presentation to activate CD8⁺ T cells are principal functions of professional antigen presenting cells. However, conventional CD4⁺ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8⁺ T cells, which proliferate and become cytotoxic in response. CD4⁺ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8⁺ T cells with low PD-1 expression. Moreover, transphagocytic CD4⁺ T cells induce protective anti-tumour immune responses by priming CD8⁺ T cells, highlighting the potential of CD4⁺ T cells as a tool for cancer immunotherapy.