PD-1 Dependent Exhaustion of CD8+ T Cells Drives Chronic Malaria
PD-1 Dependent Exhaustion of CD8+ T Cells Drives Chronic Malaria
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DOI：
10.1016/j.celrep.2013.11.002
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发表时间：
2013-12-01
期刊：
影响因子：
8.8
通讯作者：
Wykes, Michelle N.
中科院分区：
文献类型：
--
作者：
Horne-Debets, Joshua M.;Faleiro, Rebecca;Wykes, Michelle N.
疟疾是一种由疟原虫属感染引起的高度流行的疾病，感染肝细胞和红细胞。血液阶段的感染会引起毁灭性的症状，并可能持续多年。抗体和CD 4（+）T细胞被认为可以防止血液感染。然而，开发有效的疟疾疫苗存在相当大的困难，这凸显了我们对这种疾病的免疫力的不完全了解。在这里，我们使用了一个实验性啮齿动物疟疾模型来证明PD-1介导寄生虫特异性CD 8（+）T细胞的数量和功能能力减少了95%。此外，与广泛持有的观点相反，即使存在寄生虫特异性抗体和CD 4（+）T细胞，也需要寄生虫特异性CD 8（+）T细胞来控制急性和慢性血液病。我们的研究结果为慢性疟疾提供了一个分子解释，这将与未来的疟疾疫苗设计相关，当其他感染的疫苗开发有问题时，可能需要考虑。
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.