title: Efficient development of plasmodium liver stage-specific memory CD8+ T cells during the course of blood-stage malarial infection.
abstract: Immunity to Plasmodium liver stages in individuals in malaria-endemic areas is inextricably linked to concomitant blood-stage parasitemia. Although Plasmodium sporozoite infection induces measurable CD8+ T cell responses, the development of memory T cells during active erythrocytic infection remains uncharacterized. Using transgenic T cells, we assessed antigen-specific effector CD8+ T cell responses induced by normal (NorSpz) and radiation-attenuated (IrrSpz) Plasmodium yoelii sporozoites. The magnitude, phenotypic activation, and differentiation pathway of CD8+ T cells were similarly induced by NorSpz and IrrSpz. Moreover, in normal mice, memory T cells elicited after priming with NorSpz and IrrSpz generated identical recall responses after a heterologous boost strategy. Furthermore, these recall responses exhibited comparable in vivo antiparasite activity. Our results indicate that sporozoites that retain their infective capacity induce memory CD8+ T cells that are robustly recalled by secondary immunization. Thus, erythrocytic infection does not preclude the establishment of memory CD8+ T cell responses to malarial liver stages.
authors.affiliation: Department of Medical Parasitology, New York University School of Medicine, 341 E. 25th Street, New York, NY 10010, USA.
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Urvashi
authors.initials: U
authors.lastname: Rai
authors.forename: Dabeiba
authors.initials: D
authors.lastname: Bernal-Rubio
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology* / Q000528:radiation effects; D034101:Sporozoites / Q000254:growth & development / Q000276:immunology / Q000528:radiation effects; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines