Memory CD8⁺ T cells can outsource IFN-γ production but not cytolytic killing for antiviral protection.
Memory CD8⁺ T cells can outsource IFN-γ production but not cytolytic killing for antiviral protection.
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记忆 CD8™ T 细胞可以外包 IFN-γ 的生产，但不能外包杀伤细胞以实现抗病毒保护。
DOI：
10.1016/j.chom.2013.04.004
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发表时间：
2013
影响因子：
30.3
通讯作者：
Sigal,LuisJ
中科院分区：
文献类型：
--
作者：
Remakus,Sanda;Rubio,Daniel;Lev,Avital;Ma,Xueying;Fang,Min;Xu,Ren-Huan;Sigal,LuisJ
用牛痘病毒（VACV）（包含天花疫苗的病毒）免疫诱导记忆性CD 8 +T细胞，所述记忆性CD 8 +T细胞保护免受随后的人类天花或小鼠相关的肢脱病病毒（ECTV）感染。记忆性CD 8 +T细胞通过扩展成分泌抗病毒细胞因子干扰素-γ（IFN-γ）的次级效应物并通过释放因子（例如穿孔素，其使靶细胞透化）诱导细胞溶解来在很大程度上介导这些作用。我们表明，保护ECTV感染VACV免疫后依赖于初始记忆细胞的频率和能力的扩大的二级效应器杀死感染的目标穿孔素依赖性的方式。虽然IFN-γ对于抗病毒保护是必需的，但它可以由次级效应物或伴随的初级效应物CD 8 +T细胞产生，所述初级效应物CD 8 +T细胞募集到应答中。因此，在致死性病毒攻击期间，需要记忆性CD 8 +T细胞用于感染细胞的细胞溶解性杀伤，但初级效应子可通过产生IFN-γ发挥重要作用。
Immunization with vaccinia virus (VACV), the virus comprising the smallpox vaccine, induces memory CD8+T cells that protect from subsequent infections with smallpox in humans or the related ectromelia virus (ECTV) in mice. Memory CD8+T cells largely mediate these effects by expanding into secondary effectors that secrete the antiviral cytokine interferon-γ (IFN-γ) and induce cytolysis via releasing factors such as perforin, which permeabilizes target cells. We show that protection from ECTV infection after VACV immunization depends on the initial memory cell frequency and ability of expanded secondary effectors to kill infected targets in a perforin-dependent manner. Although IFN-γ is essential for antiviral protection, it can be produced by either secondary effectors or concomitant primary effector CD8+T cells recruited to the response. Thus, during lethal virus challenge, memory CD8+T cells are required for cytolytic killing of infected cells, but primary effectors can play important roles by producing IFN-γ.