T cell responses in dengue hemorrhagic fever: Are cross-reactive T cells suboptimal?
T cell responses in dengue hemorrhagic fever: Are cross-reactive T cells suboptimal?
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DOI：
10.4049/jimmunol.176.6.3821
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发表时间：
2006-03-15
影响因子：
4.4
通讯作者：
Screaton, Gavin
中科院分区：
文献类型：
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作者：
Mongkolsapaya, Juthathip;Duangchinda, Thaneeya;Screaton, Gavin
在一些热带和亚热带国家，登革热病毒感染造成越来越大的公共卫生和经济负担。登革热以若干准种传播，按血清学可分为四组或血清型。50多年前就认识到的登革热的一个有趣特征是，大多数表现出出血热的严重病例并不是由原发感染引起的。相反，它们会被不同血清型的病毒再次感染。这一观察结果给疫苗设计带来了相当大的问题，因此必须充分了解这种疾病免疫增强的机制。在这项研究中，我们检测了一个由HLA-A*24限制的T细胞表位，这是一种主要的MHC I类等位基因，在东南亚住院的急性登革热感染儿童队列中。细胞因子谱和生成该表位的T细胞的脱颗粒能力被定义并在不同的病毒血清型中进行比较。交叉反应的登革热特异性T细胞似乎表现出不理想的脱颗粒，但细胞因子的产生很高，这可能有助于发展登革出血热的血管泄漏特征。
Dengue virus infection poses a growing public health and economic burden in a number of tropical and subtropical countries. Dengue circulates as a number of quasispecies, which can be divided by serology into four groups or serotypes. An interesting feature of Dengue, recognized over five decades ago, is that most severe cases that show hemorrhagic fever are not suffering from a primary infection. Instead, they are reinfected with a virus of different serotype. This observation poses considerable problems in vaccine design, and it is therefore imperative to gain a full understanding of the mechanisms underlying this immunological enhancement of disease. In this study, we examined a T cell epitope restricted by HLA-A*24, a major MHC class I allele, in Southeast Asia in a cohort of children admitted to a hospital with acute Dengue infection. The cytokine profiles and the degranulation capacity of T cells generated to this epitope are defined and compared across different viral serotypes. Cross-reactive Dengue-specific T cells seem to show suboptimal degranulation but high cytokine production, which may contribute to the development of the vascular leak characteristic of Dengue hemorrhagic fever.