Granzyme B Expression by CD8( ) T Cells Is Required for the Development of Experimental Cerebral Malaria
Ashraful Haque, Shannon E Best, Klara Unosson, Fiona H Amante, Fabian de Labastida, Nicholas M Anstey, Gunasegaran Karupiah, Mark J Smyth, William R Heath, Christian R Engwerda
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2011
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 inductio..View full abstract
This work was supported by grants from the Australian National Health and Medical Research Council National Institutes of Health.