Prolonged Th1-like response generated by a Plasmodium yoelii-specific T cell clone allows complete clearance of infection in reconstituted mice.
In the present study, we report the ability of in vitro cultured CD4+ T cells, generated following immunization with dead blood stage P. yoelii parasites, to mediate protection against homologous challenge infection in reconstituted nude mice. P. yoelii-specific T cell line cells produced IFN-gamma after in vitro stimulation with specific antigen, and were protective when adoptively transferred into athymic nude mice. Following transfer P. yoelii-specific T cell lines into nude and SCID mice, elevated levels of nitric oxide (NO) were detected during the first week of infection at a time when parasitaemias were suppressed. However, in vivo blocking of NO production through administration of L-NMMA, an inhibitor of NO synthase, increased mortality, but did not alter the course of primary parasitaemia in P. yoelii-specific T cell line-reconstituted nude mice. In addition, a P. yoelii-specific CD4+ T cell clone, which produced IFN-gamma in vitro, afforded sterile protection via mechanisms other than NO. By ELISA, antibodies were undetectable on all but one day (day 79) post T cell clone transfer and parasite challenge, where very low levels of antibodies were detected, with some evidence of recognition of malaria proteins by Western blot. Collectively, our data suggest that T cell effector functions, independent of NO production and in the absence of high levels of parasite-specific antibodies, can contribute to sterile immunity of P. yoelii.
Amante
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FH
Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia.
Good
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MF
D019264:Adoptive Transfer; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage; D002999:Clone Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D008288:Malaria / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010967:Plasmodium yoelii / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase