Publications & Reports

CD8+ T Cells from a Novel T Cell Receptor Transgenic Mouse Induce Liver-Stage Immunity That Can Be Boosted by Blood-Stage Infection in Rodent Malaria.

Lau LS, Fernandez-Ruiz D, Mollard V, Sturm A, Neller MA, Cozijnsen A, Gregory JL, Davey GM, Jones CM, Lin YH, Haque A, Engwerda CR, Nie CQ, Hansen DS, Murphy KM, Papenfuss AT, Miles JJ, Burrows SR, de Koning-Ward T, McFadden GI, Carbone FR, Crabb BS, Heath WR
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.

Abstract

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8alpha+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

Publication

  • Journal: PLoS Pathogens
  • Published: 01/05/2014
  • Volume: 10
  • Issue: 5
  • Pagination: e1004135

Author

Health Issue

Download