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 immunity. In contrast, exposure to radiation-attenuated sporozoites (gamma 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 gamma 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 gamma spz, CD8(+) T cells expanded robustly after spz challenge and exhibited stable expression of CD44(hi) and CD45RB(lo) during protracted protection. These results establish a key role for intrahepatic T cells in long-lasting protection against malaria.
Guebre-Xabier
M
M
Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, USA.
Schwenk
R
R
Krzych
U
U
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*
D000953:Antigens, Protozoan; D017780:Malaria Vaccines