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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, Lei Shong, Fernandez-Ruiz, Daniel, Mollard, Vanessa, Sturm, Angelika, Neller, Michelle A., Cozijnsen, Anton, Gregory, Julia L., Davey, Gayle M., Jones, Claerwen M., Lin, Yi-Hsuan, Haque, Ashraful, Engwerda, Christian R., Nie, Catherine Q., Hansen, Diana S., Murphy, Kenneth M., Papenfuss, Anthony T., Miles, John J., Burrows, Scott R., de Koning-Ward, Tania, McFadden, Geoffrey I., Carbone, Francis R., Crabb, Brendan S. and Heath, William 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. 10.1371/journal.ppat.1004135

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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 CD8α+ 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: Copyright: © 2014 Lau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher: Public Library of Science
ISSN: 1553-7374
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 6 April 2014
Last Modified: 28 Apr 2020 12:44
URI: http://orca-mwe.cf.ac.uk/id/eprint/79600

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