title: Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells.
abstract: Although CD8(+) T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8(+) T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8(+) T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8(+) and CD4(+) T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8alpha(+) subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Lundie
authors.forename: Tania F
authors.initials: TF
authors.lastname: de Koning-Ward
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Davey
authors.forename: Catherine Q
authors.initials: CQ
authors.lastname: Nie
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.forename: Lei Shong
authors.initials: LS
authors.lastname: Lau
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Jose A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000953:Antigens, Protozoan / Q000276:immunology*; D001921:Brain / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008018:Life Cycle Stages; D016779:Malaria, Cerebral / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte
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