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Publication : PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria.

First Author  Horne-Debets JM Year  2013
Journal  Cell Rep Volume  5
Issue  5 Pages  1204-13
PubMed ID  24316071 Mgi Jnum  J:204141
Mgi Id  MGI:5529715 Doi  10.1016/j.celrep.2013.11.002
Citation  Horne-Debets JM, et al. (2013) PD-1 Dependent Exhaustion of CD8(+) T Cells Drives Chronic Malaria. Cell Rep 5(5):1204-13
abstractText  Malaria is a highly prevalent disease caused by infection by Plasmodium spp., which infect hepatocytes and erythrocytes. Blood-stage infections cause devastating symptoms and can persist for years. Antibodies and CD4(+) T cells are thought to protect against blood-stage infections. However, there has been considerable difficulty in developing an efficacious malaria vaccine, highlighting our incomplete understanding of immunity against this disease. Here, we used an experimental rodent malaria model to show that PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8(+) T cells. Furthermore, in contrast to widely held views, parasite-specific CD8(+) T cells are required to control both acute and chronic blood-stage disease even when parasite-specific antibodies and CD4(+) T cells are present. Our findings provide a molecular explanation for chronic malaria that will be relevant to future malaria-vaccine design and may need consideration when vaccine development for other infections is problematic.
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