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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
Open accessAbstract
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.
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This evidence was later confirmed by the formation of TRM in the liver following malaria vaccination.
“This evidence was later confirmed by the 518 formation of TRM in the liver following malaria vaccination(113, 128).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [128]
The Results section on intravenous irradiated-sporozoite vaccination reports early PbT-I activation and proliferation mainly in the spleen; divided cells appeared in the liver later. Neither that section nor the Discussion identifies those cells as liver tissue-resident memory T cells (TRM) or reports TRM formation after vaccination. Searches for TRM, resident memory, and memory found no passage establishing the claim. (LLM, conf=0.76)
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The liver as a central "hub" of the immune system: pathophysiological implications
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Metadata
- Authors
- 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., Engwerda, C. R., Nie, C. Q., Hansen, D. S., Murphy, K. M., Papenfuss, A. T., Miles, J. J., Burrows, S. R., de Koning-Ward, T., McFadden, G. I., Carbone, F. R., Crabb, B. S., & Heath, W. R.
- Affiliations
- The University of Melbourne (AU)
- QIMR Berghofer Medical Research Institute (AU)
- Burnet Institute (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Washington University in St. Louis (US)
- The University of Queensland (AU)
- Corresponding author
- Crabb, Brendan S.
- Heath, William R.
- ORCID
- 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.
- McFadden, Geoffrey I.
- Crabb, Brendan S.
- Heath, William R.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-05-22
- Volume
- 10
- Issue
- 5
- Pages
- e1004135
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC4031232
- OpenAlex
- W2123955674
- Cited by
- 99
- References
- 0
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 15 · 2016: 9 · 2015: 15 · 2014: 2
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- Monash University Research Portal (Monash University) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Medical Research Council
- Australian Research Council (CE140100011, DP130102481)
- National Health and Medical Research Council (CE140100011, 1059861, 1016629)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CD8+ T cells, Plasmodium berghei ANKA, rodent malaria, liver-stage immunity, blood-stage infection, CD8α+ dendritic cells, T cell priming, spleen, Plasmodium yoelii, Plasmodium chabaudi, malaria vaccine design
- MeSH terms
- Animals, Anopheles, Blood, Cells, Cultured, Immunization, Secondary, Life Cycle Stages, Liver, Malaria, Male, Mice, Inbred C57BL, Mice, Transgenic, Plasmodium berghei, Plasmodium yoelii, Receptors, Antigen, T-Cell, Plasmodium chabaudi, CD8-Positive T-Lymphocytes, Adoptive Transfer, Sporozoites, Mice
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