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

Lei Shong Lau, Daniel Fernandez-Ruiz, Vanessa Mollard, Angelika Sturm, Michelle A Neller, Anton Cozijnsen, Julia Louise Gregory, Gayle M Davey, Claerwen M. Jones, Yi-Hsuan Lin, Ashraful K M Nazmul Haque, Christian R Engwerda, Catherine Q Nie, Diana Hansen, Kenneth M Murphy, Anthony Troy Papenfuss, John J Miles, S R Burrows, Tania F de Koning-Ward, Geoffrey I McFaddenFrancis R Carbone, Brendan S Crabb, William R Heath

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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 CD8a+ 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.
Original languageEnglish
Article numbere1004135
Number of pages16
JournalPLoS Pathogens
Volume10
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

Lau, L. S., Fernandez-Ruiz, D., Mollard, V., Sturm, A., Neller, M. A., Cozijnsen, A., Gregory, J. L., Davey, G. M., Jones, C. M., Lin, Y-H., Haque, A. K. M. N., Engwerda, C. R., Nie, C. Q., Hansen, D., Murphy, K. M., Papenfuss, A. T., Miles, J. J., Burrows, S. R., de Koning-Ward, T. F., ... Heath, W. R. (2014). 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. PLoS Pathogens, 10(5), [e1004135]. https://doi.org/10.1371/journal.ppat.1004135