Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions
Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions
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DOI：
10.1073/pnas.0811250106
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发表时间：
2009-05-05
影响因子：
11.1
通讯作者：
Chen, Zheng W.
中科院分区：
文献类型：
--
作者：
Huang, Dan;Chen, Crystal Y.;Chen, Zheng W.
V γ 2V δ 2t效应细胞对肺部传染病具有保护作用的可能性尚未得到检验。我们最近证明，单剂量(E)-4-羟基-3-甲基-但-2-烯基焦磷酸（HMBPP）加IL-2治疗可以诱导肺中V γ 2V δ 2t效应细胞的长时间积累。本研究表明，在吸入鼠疫耶尔森菌感染后，延迟给药HMBPP/IL-2诱导V γ 2V δ 2 T细胞显著扩增，但未能控制细胞外鼠疫细菌复制/感染。令人惊讶的是，尽管没有感染控制，HMBPP/IL-2治疗后V γ 2V δ 2 T细胞的扩增导致肺部吸入性鼠疫病变的衰减。在没有或轻度鼠疫病变的肺组织中，hmbpp激活的V γ 2V δ 2t细胞在小血管周围的肺间质和气道黏膜中积聚并定位。这些浸润的V γ 2V δ 2 T细胞产生FGF-7，一种对抗组织损伤的稳态介质。相比之下，葡萄糖加IL-2或单独葡萄糖处理的对照猕猴在大多数肺叶中表现出严重的出血和坏死，肺组织中没有或很少检测到V γ 2V δ 2t细胞。这一发现与循环的V γ 2V δ 2t细胞可以运输到肺部，以维持体内平衡，防止感染中的组织损伤的范式一致。
The possibility that V gamma 2V delta 2 T effector cells can confer protection against pulmonary infectious diseases has not been tested. We have recently demonstrated that single-dose (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2 treatment can induce prolonged accumulation of V gamma 2V delta 2 T effector cells in lungs. Here, we show that a delayed HMBPP/IL-2 administration after inhalational Yersinia pestis infection induced marked expansion of V gamma 2V delta 2 T cells but failed to control extracellular plague bacterial replication/infection. Surprisingly, despite the absence of infection control, expansion of V gamma 2V delta 2 T cells after HMBPP/IL-2 treatment led to the attenuation of inhalation plague lesions in lungs. Consistently, HMBPP-activated V gamma 2V delta 2 T cells accumulated and localized in pulmonary interstitials surrounding small blood vessels and airway mucosa in the lung tissues with no or mild plague lesions. These infiltrating V gamma 2V delta 2 T cells produced FGF-7, a homeostatic mediator against tissue damages. In contrast, control macaques treated with glucose plus IL-2 or glucose alone exhibited severe hemorrhages and necrosis in most lung lobes, with no or very few V gamma 2V delta 2 T cells detectable in lung tissues. The findings are consist with the paradigm that circulating V gamma 2V delta 2 T cells can traffic to lungs for homeostatic protection against tissue damages in infection.