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Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria
Citation
Haque, A and Best, SE and Unosson, K and Amante, FH and de Labastida, F and Anstey, NM and Karupiah, G and Smyth, MJ and Heath, WR and Engwerda, CR, Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria, Journal of Immunology, 186, (11) pp. 6148-56. ISSN 0022-1767 (2011) [Refereed Article]
Copyright Statement
Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved.
DOI: doi:10.4049/jimmunol.1003955
Abstract
Parasite burden predicts disease severity in malaria and risk of death in cerebral malaria patients. In murine experimental cerebral malaria (ECM), parasite burden and CD8(+) T cells promote disease by mechanisms that are not fully understood. We found that the majority of brain-recruited CD8(+) T cells expressed granzyme B (GzmB). Furthermore, gzmB(-/-) mice harbored reduced parasite numbers in the brain as a consequence of enhanced antiparasitic CD4(+) T cell responses and were protected from ECM. We showed in these ECM-resistant mice that adoptively transferred, Ag-specific CD8(+) T cells migrated to the brain, but did not induce ECM until a critical Ag threshold was reached. ECM induction was exquisitely dependent on Ag-specific CD8(+) T cell-derived perforin and GzmB, but not IFN-γ. In wild-type mice, full activation of brain-recruited CD8(+) T cells also depended on a critical number of parasites in this tissue, which in turn, was sustained by these tissue-recruited cells. Thus, an interdependent relationship between parasite burden and CD8(+) T cells dictates the onset of perforin/GzmB-mediated ECM.
Item Details
Item Type: | Refereed Article |
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Keywords: | Malaria, granzyme B, CD8 T lymphocytes, protection |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Immunology |
Research Field: | Cellular immunology |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Karupiah, G (Associate Professor Guna Karupiah) |
ID Code: | 107815 |
Year Published: | 2011 |
Web of Science® Times Cited: | 135 |
Deposited By: | Medicine |
Deposited On: | 2016-03-24 |
Last Modified: | 2017-11-07 |
Downloads: | 0 |
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