Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection

Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection
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DOI:
10.1073/pnas.1202143109
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发表时间:
2012-06-19
影响因子:
11.1
通讯作者:
Sigal, Luis J.
Sigal, Luis J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fang, Min;Siciliano, Nicholas A.;Sigal, Luis J.

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CD4(+) T细胞通常被认为是免疫反应的助手和调节器。虽然已经描述了细胞溶解CD4(+) T细胞,但在病毒感染过程中产生的细胞是否在病毒控制中起作用仍然未知。本研究表明,在急性感染与人类天花病毒同系物的小鼠感染时,耐药小鼠的引流淋巴结和肝脏中的大量CD4(+) T细胞具有细胞毒性表型。我们还表明,这些细胞在体内以穿孔素依赖的方式杀死靶标,CD4(+) T细胞中穿孔素特异性缺乏的小鼠对病毒的控制受损。因此,穿孔素依赖性CD4(+) t细胞杀伤感染细胞是抗病毒防御的重要机制。
CD4(+) T cells are generally regarded as helpers and regulators of the immune response. Although cytolytic CD4(+) T cells have been described, whether those generated during the course of a viral infection play a role in virus control remains unknown. Here we show that during acute infection with ectromelia virus, the mouse homolog of the human virus of smallpox, large numbers of CD4(+) T cells in the draining lymph node and liver of resistant mice have a cytotoxic phenotype. We also show that these cells kill targets in vivo in a perforin-dependent manner and that mice with specific deficiency of perforin in CD4(+) T cells have impaired virus control. Thus, perforin-dependent CD4(+) T-cell killing of infected cells is an important mechanism of antiviral defense.