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Elimination of P. berghei liver stages is independent of Fas (CD95/Apo‐I) or perforin‐mediated cytotoxicity

1997; Wiley; Volume: 19; Issue: 3 Linguagem: Inglês

10.1046/j.1365-3024.1997.d01-190.x

1365-3024

John Renggli, Michael Hahne, Hugues Matile, Bruno Betschart, Jürg Tschopp, G Corradin,

Parasites and Host Interactions

Immunization of mammals with irradiated malaria sporozoites protects from a subsequent contact with the parasite. Protective immunity is directed against the pre‐erythrocytic stages of the parasite, sporozoites and liver stages. Specific antibodies neutralize part of the infectious sporozoites injected by the mosquito vector, while liver stages are the target of a cellular immune response which is mediated by T cells. In this study, we evaluated the T‐cell dependent protection induced by the injection of P. berghei irradiated sporozoites and the contribution of perforin and of the receptor/ligand system CD95/CD95L, two T cell‐dependent mechanisms known to mediate elimination of target cells. Wild type, perforin deficient, CD95 mutant, CD95L mutant and perforin deficient/CD95L mutant mice were immunized with P. berghei irradiated sporozoites and submitted to a challenge with infectious sporozoites. All mice immunized with P. berghei irradiated sporozoites were protected against a sporozoite challenge, including perforin deficient/CD95L mutant animals. These results indicate that T cells do not kill malaria‐infected hepatocytes via one of the known pathways, but rather that activated parasite‐specific T cells produce cytokines which activate in cascade other mechanisms responsible for the intracellular elimination of the parasite.