The relative contribution of antibodies, CD4+ and CD8+ T cells to sporozoite-induced protection against malaria.
Protective immunity against Plasmodium yoelii, induced by sporozoite immunization, was investigated using a quantitative method based on the measurement of plasmodial ribosomal RNA in the liver of sporozoite-challenged mice. The relative importance of the different immune mechanisms induced by sporozoite immunization was determined by evaluating quantitatively the anti-parasite activity of antibodies, CD4+ and CD8+ T cells. The role of antibodies was determined by passive transfer of immune sera to naive mice. The transfer to mice of sera obtained after a single immunizing dose reduced the liver stages by 47%. The respective contribution of CD4+ and CD8+ T-cell subsets was determined in B10 (H-2b) mice, treated with a monoclonal antibody (mAb) which inhibits B-cell maturation, and subsequently immunized once with irradiated sporozoites. These mice produced low levels of anti-sporozoite antibodies, but were capable of inhibiting the development of liver stages as efficiently as non-manipulated immunized mice. Administration of either anti-CD4 or anti-CD8 mAb to these mice, did not significantly decrease their capacity to inhibit the development of liver stages. We only observed a significant loss of immunity when the mice were depleted in vivo of both CD4+ and CD8+ T cells. In contrast to earlier studies, we found that the induction of protective immunity is not a phenomenon restricted to a few strains of mice having a particular genetic make-up. The apparent non-responsiveness observed in some strains of mice can be overcome by using larger immunizing doses.
Rodrigues
M
M
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York 10010.
Nussenzweig
R S
RS
Zavala
F
F
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens; D005260:Female; D006239:Haplotypes; D007116:Immunization, Passive; D008099:Liver / Q000737:chemistry; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000276:immunology; D012335:RNA, Ribosomal / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D000913:Antibodies, Protozoan; D016827:CD8 Antigens; D012335:RNA, Ribosomal