Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection.
Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection.
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DOI：
10.4049/jimmunol.1200571
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Dutton RW
中科院分区：
文献类型：
--
作者：
Hamada H;Bassity E;Flies A;Strutt TM;Garcia-Hernandez Mde L;McKinstry KK;Zou T;Swain SL;Dutton RW
我们之前已经证明，注射4至8 × 106个体外产生的Tc 1或Tc 17 CD 8+效应物可保护用致死剂量的PR 8-OVAI攻击的小鼠。病毒载量、肺损伤和肺功能丧失都在转移后减少。体重减轻，生存率提高。我们在此试图界定这种保护的机制。CD 8+效应子表现出多种效应子活性、穿孔素、FasL和TRAIL介导的细胞毒性、多种细胞因子（IL-2、IL-4、IL-5、IL-9、IL-10、IL-17、IL-21、IL-22、IFN-γ和TNF）和趋化因子（CCL 3、CCL 4、CCL 5、CXCL 9和CXCL 10）的分泌。在感染之前，将CD 8+效应物转移到受体中，增强了宿主嗜中性粒细胞、NK细胞、巨噬细胞和B细胞的募集。所有这些事件都有可能防止病毒感染。然而，去除这些潜在机制中的任何一种都不会对保护产生影响。即使同时去除宿主T细胞、宿主B细胞和宿主嗜中性粒细胞并消除供体细胞中穿孔素介导的裂解机制，也未能降低它们的保护能力。我们的结论是，CD 8+效应T细胞可以通过大量的冗余机制来保护免受病毒感染的致命影响。
We have previously shown that mice challenged with a lethal dose of PR8-OVAI are protected by injection of 4 to 8 × 106 in vitro - generated Tc1 or Tc17 CD8+ effectors. Viral load, lung damage and loss of lung function are all reduced following transfer. Weight loss is reduced and survival increased. We sought here to define the mechanism of this protection. CD8+ effectors exhibit multiple effector activities, perforin-, FasL- and TRAIL- mediated cytotoxicity, secretion of multiple cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-17, IL-21, IL-22, IFN-γ and TNF) and chemokines (CCL3, CCL4, CCL5, CXCL9 and CXCL10). Transfer of CD8+ effectors into recipients, prior to infection, elicits enhanced recruitment of host neutrophils, NK cells, macrophages, and B cells. All of these events have the potential to protect against viral infections. Removal of any one, however, of these potential mechanisms was without effect on protection. Even the simultaneous removal of host T cells, host B cells and host neutrophils combined with the elimination of perforin mediated lytic mechanisms in the donor cells failed to reduce their ability to protect. We conclude that CD8+ effector T cells can protect against the lethal effects of viral infection by means of a large number of redundant mechanisms.
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DOI：
10.1084/jem.141.6.1376
发表时间：
1975-06-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1084/jem.189.2.423
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Dutton RW
DOI：
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发表时间：
2007-09-03
期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Dutton, RW