Memory phenotype CD8+ T cells persist in livers of mice protected against malaria by immunization with attenuatedPlasmodium bergheisporozoites

Abstract

Natural exposure to Plasmodium parasites induces short-lived protective immunity. In contrast, exposure to radiation-attenuated sporozoites (γ spz) promotes long-lasting protection that is in part mediated by CD8+ T cells that target exoerythrocytic stage antigens. The mechanisms underlying the maintenance of long-lasting protection are currently unclear. The liver is a repository of Plasmodium antigens and may support the development and / or homing of memory T cells. While activated CD8+ T cells are presumed to die in the liver, the fate of anti-Plasmodium CD8+ T cells remains unknown. We propose that inflammatory conditions in the liver caused by Plasmodium parasites may allow some effector CD8+ T cells to survive and develop into memory cells. To support this hypothesis, in this initial study we demonstrate that liver mononuclear cells from P. berghei γ spz-immune mice transferred protection to naive recipients and moreover, that CD4+ and CD8+ T cells responded to Plasmodium antigens by up-regulating activation / memory markers. While CD4+ T cells under went a transient activation following immunization with γ spz, CD8+ T cells expanded robustly after spz challenge and exhibited stable expression of CD44hi and CD45RBlo during protracted protection. These results establish a key role for intrahepatic T cells in long-lasting protection against malaria.