Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria

Haque, Ashraful, Best, Shannon E., Unosson, Klara, Amante, Fiona H., de Labastida, Fabian, Anstey, Nicholas M., Karupiah, Gunasegaran, Smyth, Mark J., Heath, William R. and Engwerda, Christian R. (2011) Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. Journal of Immunology, 186 11: 6148-6156. doi:10.4049/jimmunol.1003955


Author Haque, Ashraful
Best, Shannon E.
Unosson, Klara
Amante, Fiona H.
de Labastida, Fabian
Anstey, Nicholas M.
Karupiah, Gunasegaran
Smyth, Mark J.
Heath, William R.
Engwerda, Christian R.
Title Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria
Formatted title
Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2011-06-01
Year available 2011
Sub-type Article (original research)
DOI 10.4049/jimmunol.1003955
Open Access Status Not yet assessed
Volume 186
Issue 11
Start page 6148
End page 6156
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted 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. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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