Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection
Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection
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DOI：
10.1073/pnas.1401662111
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发表时间：
2014-05-20
影响因子：
11.1
通讯作者：
Brooks, David
中科院分区：
文献类型：
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作者：
Osokine, Ivan;Snell, Laura M.;Brooks, David
CD4 T 细胞在持续性病毒感染过程中发挥着协调、维持和潜在再生抗病毒免疫的核心作用。尽管持续感染期间不断变化的免疫环境重塑了已建立的 CD4 T 细胞反应，但在持续感染期间启动的初始 CD4 T 细胞的命运尚不清楚。我们证明，与感染开始时形成鲜明对比的是，在已建立的持续感染期间启动的病毒特异性 CD4 T 细胞产生 Th1 反应、在外周组织中有效积累以及几乎完全分化为滤泡辅助 T 细胞的能力减弱。与抑制 Th1 和增强 Tfh 分化一致，在已建立的持续感染期间启动的病毒特异性 CD4 T 细胞为 B 细胞提供帮助，但对 CD8 T 细胞的帮助有限。 Th1 从头生成和组织分布的抑制是由慢性 I 型干扰素 (IFN-I) 产生介导的，并且通过在 CD4 T 细胞启动过程中阻断 IFN-I 信号传导可以有效恢复。因此，我们建立了在已建立的持续病毒感染期间慢性 IFN-I 信号传导的抑制功能和免疫调节机制。
CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. Although the evolving immune environment during persistent infection reshapes established CD4 T-cell responses, the fate of naive CD4 T cells primed in the midst of persistent infection is unclear. We demonstrate that, in marked contrast to the onset of infection, virus-specific CD4 T cells primed during an established persistent infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, virus-specific CD4 T cells primed during the established persistent infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established persistent virus infection.