Direct processing and presentation of antigen from malaria sporozoites by professional antigen-presenting cells in the induction of CD8 T-cell responses.
Irradiated malaria sporozoites induce better protection than viable untreated sporozoites. We observed early differences between irradiated and viable untreated sporozoites in priming responses in vivo to a protective CD8 T-cell epitope, pb9, of the circumsporozoite protein of Plasmodium berghei. Sporozoites were processed for MHC class I presentation by dendritic cells (DC) to prime pb9-specific IFN-gamma-producing CD8 T cells. DC pulsed with untreated and irradiated sporozoites were similarly capable of priming central memory T-cell responses, detectable by the IFN-gamma cultured ELISPOT assay. However, irradiation significantly enhanced sporozoites' ability to prime effector T-cell responses detectable by the IFN-gammaex vivo ELISPOT assay. Irradiation also enhanced the ability of splenic APC to process and present sporozoites in order to re-stimulate pb9-specific polyclonal and clonal T-cell responses. Sporozoites did not stimulate T cells in the absence of APC. Over-irradiation decreased the sporozoites' T-cell stimulating capacity in vitro at high parasite doses, which may indicate that an optimal irradiation dose is necessary to induce protective immunity by sporozoite inoculation. The induction of sporozoite-specific CD8 T-cell responses without the need for liver stage infection identifies a potentially important mechanism in the development of pre-erythrocytic immunity.
Plebanski
Magdalena
M
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, UK. mplebans@ari.unimelb.edu.au
Hannan
Carolyn M
CM
Behboudi
Shahriar
S
Flanagan
Katie L
KL
Apostolopoulos
Vasso
V
Sinden
Robert E
RE
Hill
Adrian V S
AV
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D034101:Sporozoites / Q000276:immunology* / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma