Human T clones reactive to the sexual stages of Plasmodium falciparum malaria. High frequency of gamete-reactive T cells in peripheral blood from nonexposed donors.
Malarial gametocytes, which are taken up by mosquitoes during a blood meal, develop in the gut of the mosquito into gametes. Gametes and gametocytes contain the target antigens of transmission-blocking immunity. Here, we show that the peripheral blood of nonexposed donors contains Plasmodium falciparum gamete-reactive T cells at frequencies ranging from 1/300 to 1/4000. Studies on long-term clones demonstrated that these cells often recognized antigens shared between gametes and asexual stage parasites or even between heterologous gametes, although it has been possible to derive a P. falciparum gamete-specific T clone. The T clones examined were T3+, T4+, T8-, and either HLA-DR- or HLA-DQ-restricted. They responded to gametes by both proliferation and the secretion of gamma-interferon. The gamete-specific clone and other asexual cross-reactive clones examined could be stimulated in vitro by a preparation of mature gametocytes within RBC, but not by RBC alone, suggesting that gametocytes are immunogenic or can become immunogenic for T cells in vivo. The significance of these observations to mosquito transmission of malaria and development and application of a gamete vaccine are discussed.
D000328:Adult; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes; D005854:Germ Cells / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D010963:Plasmodium falciparum / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D006680:HLA Antigens; D008222:Lymphokines