Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection.

Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection.
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DOI:
10.1126/science.1208421
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发表时间:
2011-11-11
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Zuniga EI
Zuniga EI
中科院分区:
其他
文献类型:
--
作者:
Harker JA;Lewis GM;Mack L;Zuniga EI

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在人类和小鼠的慢性病毒感染期间,多种抑制性分子创造了深刻的免疫抑制环境。因此,在这种情况下获得有效豁免是一项挑战。在这里,我们报告说,在小鼠慢性病毒感染,白细胞介素-6(IL-6)产生的抗辐射细胞在一个双相的方式,与晚期IL-6是绝对必要的病毒控制。潜在的机制涉及病毒特异性CD 4 T细胞上的IL-6信号传导,其在慢性病毒感染的晚期而非早期引起转录因子Bcl 6的上调和增强的T滤泡辅助(Tfh)细胞应答。这导致生发中心反应的升级和抗体应答的改善。我们的研究结果揭示了一种抗病毒策略,有助于安全地解决体内持续感染。
Multiple inhibitory molecules create a profoundly immunuosuppressive environment during chronic viral infections in humans and mice. Therefore, eliciting effective immunity in this context represents a challenge. Here we report that during a murine chronic viral infection, interleukin-6 (IL-6) was produced by irradiation resistant cells in a biphasic manner, with late IL-6 being absolutely essential for viral control. The underlying mechanism involved IL-6 signaling on virus-specific CD4 T cells that caused up-regulation of the transcription factor Bcl6 and enhanced T follicular helper (Tfh) cell responses at late, but not early, stages of chronic viral infection. This resulted in escalation of germinal center reactions and improved antibody responses. Our results uncover an antiviral strategy that helps to safely resolve a persistent infection in vivo.
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