CD8⁺ T cells eliminate liver-stage Plasmodium berghei parasites without detectable bystander effect

Immunization with attenuated Plasmodium sporozoites 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 two Plasmodium berghei strains, 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.