Pulmonary dendritic cells and alveolar macrophages are regulated by γδ T cells during the resolution of S. pneumoniae-induced inflammation
Pulmonary dendritic cells and alveolar macrophages are regulated by γδ T cells during the resolution of S. pneumoniae-induced inflammation
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DOI：
10.1002/path.2149
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发表时间：
2007-05-01
影响因子：
7.3
通讯作者：
Kaye, P. M.
中科院分区：
文献类型：
--
作者：
Kirby, A. C.;Newton, D. J.;Kaye, P. M.
γ δ T细胞通常与粘膜和上皮部位结合，实现多种免疫调节功能。虽然肺γ δ T细胞具有良好的促炎活性，但其在肺部炎症消退中的潜在作用尚未详细探索。事实上，鉴于最大限度地减少炎症的重要性，驱动肺部炎症消退的细胞机制知之甚少。使用急性肺炎链球菌介导的肺部炎症的小鼠模型，我们现在表明细菌清除后炎症的消退与γ δ T细胞数量增加> 30倍相关。尽管炎症最终在TCR δ（-/-）小鼠中消退，但肺泡巨噬细胞和肺树突状细胞数量的增加以及TCR δ（-/-）小鼠肺中形成良好的肉芽肿的出现一起表明γ δ T细胞在调节单核吞噬细胞数量中的作用。离体，肺泡巨噬细胞和肺树突状细胞对肺γ δ T细胞介导的细胞毒性敏感，这是首次证明针对树突状细胞群体的这种活性。这些发现支持了一种模型，即γ δ T细胞的扩增有助于将单核吞噬细胞数量恢复到稳态水平，保护肺部免受不适当炎症的影响。版权所有（c）2007大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
gamma delta T cells commonly associate with mucosal and epithelial sites, fulfilling a variety of immunoregulatory functions. While lung gamma delta T cells have well-characterized proinflammatory activity, their potential role in the resolution of lung inflammation has yet to be explored in any detail. Indeed, given the importance of minimizing inflammation, the cellular mechanisms driving the resolution of lung inflammation are poorly understood. Using a murine model of acute Streptococcus pneumoniae-mediated lung inflammation, we now show that resolution of inflammation following bacterial clearance is associated with a > 30-fold increase in gamma delta T-cell number. Although inflammation eventually resolves in TCR delta(-/-) mice, elevated numbers of alveolar macrophages and pulmonary dendritic cells, and the appearance of well-formed granulomas in lungs of TCR delta(-/-) mice, together indicated a role for gamma delta T cells in regulating mononuclear phagocyte number. Ex vivo, both alveolar macrophages and pulmonary dendritic cells were susceptible to lung gamma delta T cell-mediated cytotoxicity, the first demonstration of such activity against a dendritic cell population. These findings support a model whereby expansion of gamma delta T cells helps restore mononuclear phagocyte numbers to homeostatic levels, protecting the lung from the consequences of inappropriate inflammation. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.