title: Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.
abstract: In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection.
authors.affiliation: Department of Defense Malaria Vaccine Program, Naval Medical Research Institute, Bethesda, MD 20889-5055.
authors.forename: M
authors.initials: M
authors.lastname: Sedegah
authors.forename: B K
authors.initials: BK
authors.lastname: Sim
authors.forename: C
authors.initials: C
authors.lastname: Mason
authors.forename: T
authors.initials: T
authors.lastname: Nutman
authors.forename: A
authors.initials: A
authors.lastname: Malik
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Ochola
authors.forename: D
authors.initials: D
authors.lastname: Koech
authors.forename: B
authors.initials: B
authors.lastname: Were
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D016827:CD8 Antigens; D016207:Cytokines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan