Batf3 deficiency proves the pivotal role of CD 8α + dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites

Summary Increasing evidence indicates that hepatic CD 8α + dendritic cells ( DC s) are important antigen cross‐presenting cells ( APC ) involved in the priming of protective CD 8 + T‐cell responses induced by live‐attenuated Plasmodium sporozoites. Experimental proof for a critical role of CD 8α + DC s in protective pre‐erythrocytic malaria immunizations has pivotal implications for vaccine development, including improved vectored subunit vaccines. Employing Batf3 −/− mice, which lack functional CD 8α + DC s, we demonstrate that deficiency of these particular APC s completely abolishes protection and corresponding signatures of vaccine‐induced immunity. We show that in wild‐type, but not in Batf3 −/− , mice CD 8α + DC s accumulate in the liver after immunization with live irradiation‐attenuated P. berghei sporozoites. IFN ‐γ production by Plasmodium antigen‐specific CD 8 + T cells is dependent on functional Batf3. In addition, our results demonstrate that the dysfunctional cDC ‐ CD 8+ T‐cell axis correlates with MHC class II upregulation on splenic CD 8α − DC s. Collectively, these findings underscore the essential role of CD 8α + DC s in robust protection induced by experimental live‐attenuated malaria vaccines.