CD8 T cells use IFN-γ to protect against the lethal effects of a respiratory poxvirus infection.
CD8 T cells use IFN-γ to protect against the lethal effects of a respiratory poxvirus infection.
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DOI：
10.4049/jimmunol.1400256
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发表时间：
2014-06-01
期刊：
影响因子：
--
通讯作者：
Salek-Ardakani S
中科院分区：
文献类型：
--
作者：
Goulding J;Abboud G;Tahiliani V;Desai P;Hutchinson TE;Salek-Ardakani S
CD8T细胞是对许多病毒感染免疫的关键组成部分。他们通过利用一系列效应器机制实现这一点，但确切地说，需要哪些成分/S来预防呼吸道正痘病毒感染仍不清楚。利用小鼠呼吸道痘苗病毒感染模型，我们可以特异性地确定穿孔素、TRAIL和干扰素-γ介导的通路在预防病毒诱导的发病率和死亡率中的相对贡献。出乎意料的是，我们观察到对死亡的保护是由干扰素-γ介导的，而不涉及穿孔素或TRAIL依赖的途径。肺组织中干扰素-γ基因和蛋白的表达在感染后3~6天达到高峰。这种增强的反应与肺中出现病毒特异性CD8T细胞和停止减肥相一致。转移实验表明，CD8T细胞自主表达的干扰素-γ抑制病毒诱导的肺病理，向内脏组织扩散，是清除病毒所必需的。最重要的是，我们证明了CD8T细胞来源的干扰素-γ足以在缺乏CD4T细胞和B淋巴细胞的情况下保护小鼠。因此，我们的发现揭示了一种以前未被认识的机制，即效应器CD8T细胞对高度毒力的呼吸道正痘病毒感染提供保护。
CD8 T cells are a key component of immunity to many viral infections. They achieve this through utilizing an array of effector mechanisms, but precisely which component/s are required for protection against a respiratory Orthopoxvirus infection remains unclear. Using a model of respiratory vaccinia virus (VACV) infection in mice, we could specifically determine the relative contribution of perforin, TRAIL, and IFN-γ mediated pathways in protection against virus induced morbidity and mortality. Unexpectedly, we observed that protection against death was mediated by IFN-γ without any involvement of the perforin or TRAIL-dependent pathways. IFN-γ mRNA and protein levels in the lung peaked between days 3 and 6 post infection. This enhanced response coincided with the emergence of virus-specific CD8 T cells in the lung and the cessation of weight loss. Transfer experiments indicated that CD8 T cell autonomous expression of IFN-γ restricts virus induced lung pathology, dissemination to visceral tissues, and is necessary for clearance of virus. Most significantly, we show that CD8 T cell derived IFN-γ is sufficient to protect mice in the absence of CD4 and B-lymphocytes. Thus our findings reveal a previously unappreciated mechanism by which effector CD8 T cells afford protection against a highly virulent respiratory Orthopoxvirus infection.
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DOI：
10.4049/jimmunol.1200571
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Bassity E;Flies A;Strutt TM;Garcia-Hernandez Mde L;McKinstry KK;Zou T;Swain SL;Dutton RW
通讯作者：
Dutton RW
DOI：
10.1073/pnas.89.11.4825
发表时间：
1992-06-01
影响因子：
11.1
作者：
CHANG, HW;WATSON, JC;JACOBS, BL
通讯作者：
JACOBS, BL
DOI：
10.4269/ajtmh.1985.34.781
发表时间：
1985-01-01
影响因子：
3.3
作者：
ARITA, I;JEZEK, Z;RUTI, K
通讯作者：
RUTI, K
影响因子：
5.4
作者：
KARUPIAH, G;FREDRICKSON, TN;BULLER, RML
通讯作者：
BULLER, RML
影响因子：
56.9
作者：
KARUPIAH, G;XIE, QW;MACMICKING, JD
通讯作者：
MACMICKING, JD