title: Blood-stage Plasmodium berghei infection generates a potent, specific CD8+ T-cell response despite residence largely in cells lacking MHC I processing machinery.
abstract: Murine cerebral malaria is a complex disease caused by Plasmodium berghei ANKA infection. Several cell types, including CD8(+) T cells, are essential effectors of disease. Although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic T lymphocytes (CTL) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. Our studies show that there is a dramatic primary parasite-specific CTL response, akin to viral immunity, reaching approximately 30% of splenic CD8(+) T cells, with many producing interferon-γ and tumor necrosis factor-α. These cells express granzyme B and other markers of specific responders, are cytolytic, and respond to a broad array of major histocompatibility complex (MHC) I-restricted epitopes, 5 of which are identified here. Our studies indicate that vigorous CTL responses can be induced to pathogens even when they largely reside in red blood cells, which lack MHC I processing machinery.
authors: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors: Lei Shong
authors: LS
authors: Lau
authors: Daniel
authors: D
authors: Fernandez Ruiz
authors: Gayle M
authors: GM
authors: Davey
authors: Tania F
authors: TF
authors: de Koning-Ward
authors: Anthony T
authors: AT
authors: Papenfuss
authors: Francis R
authors: FR
authors: Carbone
authors: Andrew G
authors: AG
authors: Brooks
authors: Brendan S
authors: BS
authors: Crabb
authors: William R
authors: WR
authors: Heath
mesh_terms: D000818:Animals; D040881:CD11a Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology*; D052939:Schizonts / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D040881:CD11a Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D000939:Epitopes; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes