Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells.

Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells.
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DOI:
10.1084/jem.20101773
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发表时间:
2011-05-09
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Brooks DG
Brooks DG
中科院分区:
其他
文献类型:
--
作者:
Fahey LM;Wilson EB;Elsaesser H;Fistonich CD;McGavern DB;Brooks DG

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持续性病毒感染驱动滤泡辅助性T细胞分化。 CD4 T细胞应答对于预防和控制病毒感染至关重要;然而,在许多持续性病毒感染过程中,病毒特异性CD4 T细胞活性被认为会迅速丧失。这在很大程度上是由于在病毒持续存在期间,CD4 T细胞不产生与控制急性病毒感染相关的经典Th1细胞因子这一事实所致。考虑到CD4 T细胞的辅助对于CD8 T细胞和B细胞的功能都至关重要,目前尚不清楚CD4 T细胞如何会失去反应性但却能继续维持对持续性病毒复制的长期控制。我们现在证明,CD4 T细胞功能不会因病毒持续存在而消失。相反,病毒的持续存在和长时间的T细胞受体刺激逐渐使CD4 T细胞的发育从急性感染期间诱导的Th1反应转向滤泡辅助性T细胞。重要的是,这种持续的CD4 T细胞功能对于维持免疫以及最终帮助控制持续性病毒感染至关重要。
Persistent virus infection drives follicular T helper cell differentiation. CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.
慢性病毒感染期间CD4(+)T细胞反应的损害可防止对病毒逃生突变体的中和抗体反应。
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