CD8+T Cells Eliminate Liver-Stage Plasmodium berghei Parasites without Detectable Bystander Effect

Abstract

ABSTRACTImmunization with attenuatedPlasmodiumsporozoites or viral vectored vaccines can induce protective CD8+T cells that can find and eliminate liver-stage malaria parasites. A key question is whether CD8+T cells must recognize and eliminate each parasite in the liver or whether bystander killing can occur. To test this, we transferred antigen-specific effector CD8+T cells to mice that were then coinfected with twoPlasmodium bergheistrains, only one of which could be recognized directly by the transferred T cells. We found that the noncognate parasites developed normally in these mice, demonstrating that bystander killing of parasites does not occur during the CD8+T cell response to malaria parasites. Rather, elimination of infected parasites is likely mediated by direct recognition of infected hepatocytes by antigen-specific CD8+T cells.