CD40 is required for protective immunity against liver stage Plasmodium infection.

The costimulatory molecule CD40 enhances immunity through several distinct roles in T cell activation and T cell interaction with other immune cells. In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite. Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves. Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice. Thus, protective immunity generated during immunization with fabb/f(-) was largely dependent on effective APC licensing via CD40 signaling.