MHC class I-dependent presentation of exoerythrocytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium berghei.
T lymphocytes are believed to play a major role in protection against malaria. Previous experiments using in vivo depletion of CD8+ T cells, reconstitution with CD8+ T splenic cells, and adoptive transfer of CD8+ CTL clones demonstrated that protection against the exoerythrocytic stage of the murine strain, Plasmodium berghei malaria, was CD8+ T cell-dependent. Despite evidence for the critical role of CD8+ CTL, neither the cellular nor the molecular requirements for CD8+ T cell induction or for recognition of malaria Ags are known. In this study, we wished to define the role of CD8+ T cells and MHC class I molecules by using the P. berghei malaria attenuated sporozoites (SPZ) protection model in beta 2-microglobulin (beta 2m) knockout (-/-) mice. In contrast to observations that beta 2m-/- mice are resistant to many infectious diseases by compensatory mechanisms involving non-class I-restricted T cells, we found that beta 2m-/- mice failed to be protected against P. berghei SPZ, although immunization with attenuated SPZ induced production of IL-2, INF-gamma, anti-circumsporozoite protein IgG, and proliferative T cells. The lack of compensatory mechanisms involving non-CD8+ T cells was particularly evident in the failure to adoptively transfer protective immunity with wild-type SPZ-immune splenic T cells. From our data it can be concluded that CD8+ T cells induced during immunization with attenuated SPZ must recognize liver-expressed Ags presented by class I molecules to engage effectively in a response leading to destruction of the malaria parasites.
White
K L
KL
Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Snyder
H L
HL
Krzych
U
U
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000469:parasitology / Q000637:transplantation; D014613:Vaccines, Attenuated / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics
D000953:Antigens, Protozoan; D015395:Histocompatibility Antigens Class I; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D001613:beta 2-Microglobulin