Memory phenotype CD8(+) T cells persist in livers of mice protected against malaria by immunization with attenuated Plasmodium berghei sporozoites

Natural exposure to Plasmodium parasites induces short-lived protective imm unity, in contrast, exposure to radiation-attenuated sporozoites (gamma spz ) promotes long-lasting protection that is in part mediated by CD8(+) T cel ls that target exoerythrocytic stage antigens. The mechanisms underlying th e maintenance of long-lasting protection are currently unclear. The liver i s a repository of Plasmodium antigens and may support the development and/o r 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 in to memory cells. To support this hypothesis, in this initial study we demon strate that liver mononuclear cells from Fl berghei gamma spz-immune mice t ransferred protection to naive recipients and moreover, that CD4(+) and CD8 (+) T cells responded to Plasmodium antigens by up-regulating activation/me mory markers. While CD4(+) T cells underwent a transient activation followi ng immunization with gamma spz, CD8(+) T cells expanded robustly after spz challenge and exhibited stable expression of CD44(h) and CD45RB(lo) during protracted protection. These results establish a key role for intrahepatic T cells in longlasting protection against malaria.