Enhancement of dendritic cell activation via CD40 ligand-expressing γδ T cells is responsible for protective immunity to Plasmodium parasites

Previous reports have shown that gamma delta T cells are important for the elimination of malaria parasites in humans and mice. However, how gamma delta T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected gamma delta T-cell-deficient (TCR delta-KO) mice and control wild-type mice with Plasmodium berghei XAT, which is a nonlethal strain. Although infected red blood cells were eliminated within 30 d after infection, TCRd-KO mice could not clear the infected red blood cells, showed high parasitemia, and eventually died.Therefore, gamma delta T cells are essential for clearance of the parasites. Here, we found that gamma delta T cells play a key role in dendritic cell activation after Plasmodium infection. On day 5 postinfection, gamma delta T cells produced IFN-gamma and expressed CD40 ligand during dendritic cell activation. These results suggest that gamma delta T cells enhance dendritic cell activation via IFN-gamma and CD40 ligand-CD40 signaling. This hypothesis is supported strongly by the fact that in vivo induction of CD40 signaling prevented the death of TCRd-KO mice after infection with P. berghei XAT. This study improves our understanding of protective immunity against malaria and provides insights into gamma delta T-cell-mediated protective immunity against various infectious diseases.