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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.

Original publication

DOI

10.1111/j.1440-1711.2005.01325.x

Type

Journal article

Journal

Immunol Cell Biol

Publication Date

06/2005

Volume

83

Pages

307 - 312

Keywords

Animals, Antigen Presentation, Antigen-Presenting Cells, Antigens, Protozoan, CD8-Positive T-Lymphocytes, Coculture Techniques, Dendritic Cells, Interferon-gamma, Lymphocyte Activation, Malaria, Mice, Mice, Inbred BALB C, Plasmodium berghei, Protozoan Proteins, Spleen, Sporozoites, T-Lymphocytes