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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
Keywords:Malaria, granzyme B, CD8 T lymphocytes, protection
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:107815
Year Published:2011
Web of Science® Times Cited:82
Deposited By:Medicine (Discipline)
Deposited On:2016-03-24
Last Modified:2017-11-07
Downloads:0

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