| First Author | Haque A | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 11 | Pages | 6148-56 |
| PubMed ID | 21525386 | Mgi Jnum | J:173185 |
| Mgi Id | MGI:5013517 | Doi | 10.4049/jimmunol.1003955 |
| Citation | Haque A, et al. (2011) Granzyme B Expression by CD8+ T Cells Is Required for the Development of Experimental Cerebral Malaria. J Immunol 186(11):6148-56 |
| abstractText | 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-gamma. 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. |
