Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection.
Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection.
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DOI：
10.4049/jimmunol.1000423
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发表时间：
2010-08-15
期刊：
影响因子：
--
通讯作者：
Varga SM
中科院分区：
文献类型：
--
作者：
Fulton RB;Meyerholz DK;Varga SM
调节性Foxp3+ CD4 T细胞（Tregs）可预防肺部自发性炎症，抑制过敏和哮喘反应，并有助于对吸入过敏原的耐受性。此外，Tregs先前已被证明在持续病毒感染期间抑制CD8 T细胞反应。然而，在急性呼吸道病毒感染期间，Tregs在调节适应性免疫反应中的作用知之甚少。我们发现急性呼吸道合胞病毒（RSV）感染后，Foxp3+ CD4 treg在肺引流纵隔淋巴结和肺中迅速积聚。brdu掺入研究表明，treg经历增殖，有助于其在淋巴结和肺部的积累。急性RSV感染后，肺部Tregs调节CD25表达并获得活化表型，其特征为CD11ahi、CD44hi、CD43glyco+、ICOS+和CTLA-4+。令人惊讶的是，在感染RSV之前，体内Tregs的消耗导致病毒清除延迟，同时RSV特异性CD8 T细胞募集到肺部的早期滞后。此外，Treg耗竭导致疾病严重程度加重，包括体重减轻、发病率增加和气道受限加剧。在treg缺失的小鼠中，rsv特异性CD8 T细胞共同产生IFN-γ和TNF-α的频率增加，这可能有助于提高疾病的严重程度。这些结果表明，肺Tregs通过影响肺和引流淋巴结中病毒特异性CD8 T细胞的运输和效应功能，在限制急性肺病毒感染期间的免疫病理中发挥关键作用。这是一篇被《免疫学杂志》（The Journal of Immunology, The JI）接受发表的手稿的作者版本。美国免疫学家协会，Inc. (AAI)，《免疫学杂志》的出版商，拥有这份手稿的版权。这个版本的手稿还没有被编辑或受到编辑校对的JI；因此，它可能不同于在JI上发表的最终版本（在线和印刷）。AAI （The JI）不对本作者制作的手稿版本中的错误或遗漏负责，也不对美国国立卫生研究院或任何其他第三方从该手稿衍生的任何版本中的错误或遗漏负责。该记录的最终可引用版本可在www.jimmunol.org上找到。
Regulatory Foxp3+ CD4 T cells (Tregs) prevent spontaneous inflammation in the lungs, inhibit allergic and asthmatic responses, and contribute to tolerance to inhaled allergens. Additionally, Tregs have previously been shown to suppress the CD8 T cell response during persistent virus infections. However, little is known concerning the role Tregs play in modulating the adaptive immune response during acute respiratory virus infections. We show following acute respiratory syncytial virus (RSV) infection that Foxp3+ CD4 Tregs rapidly accumulate in the lung-draining mediastinal lymph nodes and lungs. BrdU-incorporation studies indicate that Tregs undergo proliferation that contributes to their accumulation in the lymph nodes and lungs. Following an acute RSV infection, pulmonary Tregs modulate CD25 expression and acquire an activated phenotype characterized as CD11ahi, CD44hi, CD43glyco+, ICOS+, and CTLA-4+. Surprisingly, in vivo depletion of Tregs prior to RSV infection results in delayed virus clearance concomitant with an early lag in the recruitment of RSV-specific CD8 T cells into the lungs. Additionally, Treg depletion results in exacerbated disease severity including increased weight loss, morbidity, and enhanced airway restriction. In Treg-depleted mice there is an increase in the frequency of RSV-specific CD8 T cells that co-produce IFN-γ and TNF-α, which may contribute to enhanced disease severity. These results indicate that pulmonary Tregs play a critical role in limiting immunopathology during an acute pulmonary virus infection by influencing the trafficking and effector function of virus-specific CD8 T cells in the lungs and draining lymph nodes. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
32.4
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
DOI：
10.1073/pnas.192162899
发表时间：
2002-10-01
影响因子：
11.1
作者：
Lehmann, J;Huehn, J;Hamann, A
通讯作者：
Hamann, A
影响因子：
4.4
作者：
Haeryfar, SMM;DiPaolo, RJ;Yewdell, JW
通讯作者：
Yewdell, JW
DOI：
10.1084/jem.20081811
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Friedline RH;Brown DS;Nguyen H;Kornfeld H;Lee J;Zhang Y;Appleby M;Der SD;Kang J;Chambers CA
通讯作者：
Chambers CA