Activation and exhaustion of antigen-specific CD8+ T cells occur in different splenic compartments during infection with Plasmodium berghei.

The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8+ T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8+ T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8+ T cells were distinct. During infection with malaria parasites, activated CD8+ T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8+ T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8+ T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8+ T cells during infection with Plasmodium parasites and Listeria, and suggested that activation and exhaustion of specific CD8+ T cells occurred in distinct spleen compartments during infection with malaria parasites.