RRC ID 28432
著者 Horne-Debets JM, Faleiro R, Karunarathne DS, Liu XQ, Lineburg KE, Poh CM, Grotenbreg GM, Hill GR, MacDonald KP, Good MF, Renia L, Ahmed R, Sharpe AH, Wykes MN.
タイトル PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria.
ジャーナル Cell Rep
Abstract 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.
巻・号 5(5)
ページ 1204-13
公開日 2013-12-12
DOI 10.1016/j.celrep.2013.11.002
PII S2211-1247(13)00650-5
PMID 24316071
MeSH Animals CD8-Positive T-Lymphocytes / metabolism* CD8-Positive T-Lymphocytes / pathology Malaria / blood* Malaria / immunology Malaria / metabolism Mice Mice, Inbred C57BL Programmed Cell Death 1 Receptor / genetics Programmed Cell Death 1 Receptor / metabolism*
IF 8.109
引用数 86
WOS 分野 CELL BIOLOGY
リソース情報
実験動物マウス RBRC02142