Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria.
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Authors
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Fernandez-Ruiz, Daniel1, 2
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Lau, Lei Shong1
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Ghazanfari, Nazanin1, 2
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Jones, Claerwen M1
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Ng, Wei Yi1
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Davey, Gayle M1
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Berthold, Dorothee1
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Holz, Lauren1, 2
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Kato, Yu1
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Enders, Matthias H1
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Bayarsaikhan, Ganchimeg1, 3
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Hendriks, Sanne H1
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Lansink, Lianne I M4
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Engel, Jessica A4
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Soon, Megan S F4
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James, Kylie R4
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Cozijnsen, Anton5
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Mollard, Vanessa5
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Uboldi, Alessandro D6
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Tonkin, Christopher J6
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de Koning-Ward, Tania F7
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Gilson, Paul R8
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Kaisho, Tsuneyasu9
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Haque, Ashraful4
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Crabb, Brendan S8
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Carbone, Francis R1
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McFadden, Geoffrey I5
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Heath, William R10, 2
And 8 more
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1
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3000, Australia.
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(Australia)
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2
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, Victoria 3010, Australia.
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(Australia)
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3
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
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(Japan)
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4
Malaria Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.
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(Australia)
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5
School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
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(Australia)
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6
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
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(Australia)
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7
School of Medicine, Deakin University, Waurn Ponds, Victoria 3216, Australia.
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(Australia)
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8
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; and.
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(Australia)
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9
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
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(Japan)
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10
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3000, Australia; [email protected].
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(Australia)
- Type
- Published Article
- Journal
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The Journal of Immunology
- Publisher
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The American Association of Immunologists
- Publication Date
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Dec 15, 2017
- Volume
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199
- Issue
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12
- Pages
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4165–4179
- Identifiers
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DOI: 10.4049/jimmunol.1700186
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PMID: 29084838
- Source
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Medline
- License
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Unknown
Abstract
We describe an MHC class II (I-Ab)-restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4+ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human (Plasmodium falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8+ T cell-mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4+ T cells and the previously described PbT-I CD8+ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8+ DC (a subset of XCR1+ DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4+ T cell responses. Depletion of CD8+ DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4+ T cell immunity during malaria and provides evidence that CD4+ T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8+ DC.
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This record was last updated on 04/13/2018 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/29084838
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