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). pp. 1-16.

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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 ID: 45056
Item Type: Article (Research - C1)
ISSN: 1553-7374
Additional Information:

© 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.

https://creativecommons.org/licenses/by/4.0/

Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: ARC FF776174, ARC CE140100011, ARC DP130102481, NHMRC APP1016629, NHMRC APP1059861
Date Deposited: 09 Aug 2016 04:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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