文章基本信息

标题：Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions
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作者：Dan Huang ; Crystal Y. Chen ; Zahida Ali 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：18
页码：7553-7558
DOI：10.1073/pnas.0811250106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：(E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate immunotherapeutics ; lung ; macaques ; immune regulation ; clonal expansion