Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive.
Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive.
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DOI：
10.1038/icb.2010.61
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发表时间：
2011-01
影响因子：
4
通讯作者：
Mathew, Anuja
中科院分区：
文献类型：
--
作者：
Friberg, Heather;Burns, Lynne;Woda, Marcia;Kalayanarooj, Siripen;Endy, Timothy P.;Stephens, Henry A. F.;Green, Sharone;Rothman, Alan L.;Mathew, Anuja
交叉反应性记忆T细胞诱导的主要感染的四种血清型的登革病毒（DENV）被假设在二次异源DENV感染中发挥免疫病理学作用。为了确定对异源血清型的T细胞应答，我们从原代DENV免疫供体中分离出HLA-A*1101限制性表位特异性CD 8 + T细胞系。在四聚体结合和功能测定中，细胞系表现出对代表四种DENV血清型的肽变体的显著交叉反应性。许多克隆对同源和异源血清型的反应相似，在DENV-1和DENV-3表位变体之间具有显著的交叉反应性。体外刺激的T细胞系一致地显示MIP-1β >脱粒> TNFα > IFNγ的分级诱导，这依赖于激动肽的浓度。Phosphoflow分析显示ERK 1/2的肽剂量依赖性磷酸化，其与细胞溶解、脱粒以及TNFα和IFNγ的诱导相关，但与MIP-1β的产生无关。这是第一项证明自然获得性原发感染后CD 8 + T细胞的显著DENV病毒型交叉反应性的研究。我们还证明了在用同源和异源肽刺激后定性地不同的T细胞受体信号传导。我们的数据支持一种模型，即连续DENV感染的顺序影响对继发性异源DENV感染的免疫应答，从而导致不同的疾病结果。
Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to play an immunopathological role in secondary heterologous DENV infection. To define the T cell response to heterologous serotypes, we isolated HLA-A*1101-restricted epitope-specific CD8+ T cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity towards peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking cross-reactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T cell lines consistently revealed a hierarchical induction of MIP-1β > degranulation > TNFα > IFNγ, which depended on the concentration of agonistic peptide. Phosphoflow assays demonstrated peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNFα and IFNγ but not MIP-1β production. This is the first study to demonstrate significant DENV serotype-cross-reactivity of CD8+ T cells after naturally-acquired primary infection. We also demonstrate qualitatively different T cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes.
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影响因子：
3.7
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
通讯作者：
Rowland-Jones S
影响因子：
20.3
作者：
Lillard, JW;Singh, UP;McGhee, JR
通讯作者：
McGhee, JR
影响因子：
5.4
作者：
Mathew, A;Kurane, I;Rothman, AL
通讯作者：
Rothman, AL
影响因子：
6.4
作者：
Green, S;Vaughn, DW;Ennis, FA
通讯作者：
Ennis, FA
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