title: CD40 is required for protective immunity against liver stage Plasmodium infection.
abstract: The costimulatory molecule CD40 enhances immunity through several distinct roles in T cell activation and T cell interaction with other immune cells. In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite. Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves. Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice. Thus, protective immunity generated during immunization with fabb/f(-) was largely dependent on effective APC licensing via CD40 signaling.
authors: Department of Global Health, University of Washington, Seattle, WA 98195;
authors: Sara A
authors: SA
authors: Murray
authors: Department of Pathology, University of Washington, Seattle, WA 98195; and.
authors: Isaac
authors: I
authors: Mohar
authors: Seattle Biomedical Research Institute, Seattle, WA 98109.
authors: Jessica L
authors: JL
authors: Miller
authors: Department of Global Health, University of Washington, Seattle, WA 98195;
authors: Katherine J
authors: KJ
authors: Brempelis
authors: Seattle Biomedical Research Institute, Seattle, WA 98109.
authors: Ashley M
authors: AM
authors: Vaughan
authors: Department of Global Health, University of Washington, Seattle, WA 98195; Seattle Biomedical Research Institute, Seattle, WA 98109.
authors: Stefan H I
authors: SH
authors: Kappe
authors: Department of Pathology, University of Washington, Seattle, WA 98195; and crispen@u.washington.edu.
authors: Ian N
authors: IN
authors: Crispe
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D022781:Hepatocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D034101:Sporozoites / Q000737:chemistry / Q000276:immunology*; D014613:Vaccines, Attenuated
chemical_list: D019013:CD40 Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014613:Vaccines, Attenuated
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