Vg1+ gd T cells promote DC activation and CD8 T cell expansion via IL-4

Classically, dendritic cells (DC) capture pathogen material and upon activation by pathogen products (or damage), initiate adaptive immunity. Here, we describe an additional layer to this process, required when the pathogen-derived signals themselves do not provide effective DC activation. Immunisation with sporozoites from Plasmodium leads to the generation of protective anti-malarial immunity mediated by liver resident memory T (TRM) cells, in a complex response that is crucially dependent upon gd T cells. Here, we show that CD40L signals to antigen-presenting DC are CD4 T cell derived, but Vg1 gd T cells play an initiating role by providing essential IL-4 signals to DC. IL-4 acts together with IFNg to induce IL-12 and promote CD8 T cell expansion. This study shows that responses to some pathogens, such as Plasmodium, require help from innate-like T cells to pass the initiation threshold, and demonstrates the critical role of IL-4 in this process.