High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.
High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.
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DOI：
10.1371/journal.pone.0001192
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发表时间：
2007-12-05
期刊：
影响因子：
3.7
通讯作者：
Rowland-Jones S
中科院分区：
文献类型：
--
作者：
Dong T;Moran E;Vinh Chau N;Simmons C;Luhn K;Peng Y;Wills B;Phuong Dung N;Thi Thu Thao L;Hien TT;McMichael A;Farrar J;Rowland-Jones S
登革热是通过节肢动物媒介传播的最重要的人类疾病之一，登革热病毒感染的发病率一直在增加——目前世界上一半以上的人口生活在有感染风险的地区。大多数感染是无症状的，但一部分患者会出现以血浆渗漏为特征的潜在致命性休克综合征。严重形式的登革热在流行病学上与四种登革热病毒血清型中超过一种的重复感染有关。通常归因于抗体依赖性增强现象，最近的观察表明 T 细胞也可能影响疾病表型。在登革热血清型之间表现出高水平交叉反应性的病毒特异性细胞毒性 T 淋巴细胞 (CTL) 可以从继发性登革热感染急性期采集的血液样本中扩展出来。当仅鉴定出表现出显着血清型特异性的 CTL 群体时，这些在恢复期无法检测到。来自这些患者的登革热交叉反应性 CTL 克隆比血清型特异性克隆具有更高的亲合力，并产生更高水平的 1 型和某些 2 型细胞因子，其中许多细胞因子先前与登革热发病机制有关。登革热血清型交叉反应性 CTL 克隆对抗原表现出高亲和力，比血清型特异性克隆产生更高水平的炎性细胞因子。这些细胞无法从恢复期样本中扩增出来，这表明它们可能已被耗尽，这可能是激活诱导的细胞死亡的结果。这种高亲和力的交叉反应记忆CTL可能在继发感染过程中产生炎症细胞因子，导致血管渗漏的发病机制。这些细胞似乎随后被删除，留下了更具血清型特异性的记忆 CTL 池。需要进一步的研究将这些细胞观察结果与大量患者的疾病表型联系起来。如果得到证实，它们对于了解病毒特异性 CTL 在登革热发病机制中的作用具有重要意义。
Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing – over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease.
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DOI：
10.4269/ajtmh.1988.38.172
发表时间：
1988-01-01
影响因子：
3.3
作者：
BURKE, DS;NISALAK, A;SCOTT, RM
通讯作者：
SCOTT, RM
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM
影响因子：
64.8
作者：
Klenerman, P;Zinkernagel, RM
通讯作者：
Zinkernagel, RM
影响因子：
5.4
作者：
Dong, T;Boyd, D;RowlandJones, S
通讯作者：
RowlandJones, S
影响因子：
15.3
作者：
Alexander-Miller, MA;Derby, MA;Berzofsky, JA
通讯作者：
Berzofsky, JA