Direct processing and presentation of antigen from malaria sporozoites by professional antigen-presenting cells in the induction of CD8+ T-cell responses

Magdalena Plebanski, Carolyn M. Hannan, Shahriar Behboudi, Katie L. Flanagan, Vasso Apostolopoulos, Robert E. Sinden, Adrian V S Hill

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39 Citations (Scopus)

Abstract

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-γ-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-γ cultured ELISPOT assay. However, irradiation significantly enhanced sporozoites' ability to prime effector T-cell responses detectable by the IFN-γ ex 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 languageEnglish
Pages (from-to)307-312
Number of pages6
JournalImmunology and Cell Biology
Volume83
Issue number3
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

Keywords

  • Antigen-presenting cell
  • Circumsporozoite protein
  • Dendritic cell
  • Malaria

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