Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes
Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes
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DOI：
10.1016/s0002-9440(10)63504-3
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发表时间：
2003-10-01
影响因子：
6
通讯作者：
London, L
中科院分区：
文献类型：
--
作者：
Majeski, EI;Paintlia, MK;London, L
闭塞性细支气管炎机化性肺炎（BOOP）是一种以血管周围/细支气管周围白细胞浸润导致肺泡内纤维化为特征的临床综合征。我们开发了一种 BOOP 动物模型，其中感染 1 x 10(6) 噬菌斑形成单位 (PFU) 呼肠孤病毒 1/L 的 CBA/J 小鼠会出现与人类 BOOP 类似的滤泡性细支气管炎和肺泡内纤维化。在本报告中，我们证明了 T 细胞在 BOOP 相关管腔内纤维化发展中的作用。对呼肠孤病毒 1/L 感染的小鼠进行皮质类固醇治疗，在早期给药时可抑制纤维化病变的发展，而在延迟皮质类固醇给药时可促进纤维化病变的消退。此外，呼肠孤病毒1/L感染前CD4(+)或CD8(+) T细胞的耗竭也抑制了纤维化病变的发展。皮质类固醇治疗和CD4(+)或CD8(+) T细胞的耗竭也导致促炎和促纤维化细胞因子、干扰素(IFN)-γ和单核细胞趋化蛋白-1(MCP-1)的表达减少。此外，用抗 IFN-γ 的中和单克隆抗体治疗小鼠也显着抑制了纤维化的发展。总而言之，这些结果表明 T 细胞在呼肠孤病毒的发展中发挥着重要作用。 1/L 在 CBA/J 小鼠中诱导 BOOP 纤维化病变，表明 T(H)1 衍生的细胞因子，尤其是 IFN-γ，可能在纤维化病变的发展中发挥关键作用。
Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinical syndrome characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intraalveolar fibrosis. We have developed an animal model of BOOP where CBA/J mice infected with 1 x 10(6) plaque-forming units (PFU) reovirus 1/L develop follicular bronchiolitis and intraalveolar fibrosis similar to human BOOP. In this report, we demonstrate a role for T cells in the development of intraluminal fibrosis associated with BOOP. Corticosteroid treatment of reovirus 1/L-infected mice both inhibited the development of fibrotic lesions when administered early in the time-course and promoted the resolution of fibrotic lesions when corticosteroid administration was delayed. Further, the depletion of either CD4(+) or CD8(+) T cells before reovirus 1/L infection also inhibited fibrotic lesion development. Both corticosteroid treatment and depletion of CD4(+) or CD8(+) T cells also resulted in decreased expression of the proinflammatory and profibrotic cytokines, interferon (IFN)-gamma and monocyte chemoattractant protein-1 (MCP-1). Further, treatment of mice with a neutralizing monoclonal antibody to IFN-gamma also significantly inhibited the development of fibrosis. Taken together, these results suggest a significant role for T cells in the development of reovirus; 1/L-induced BOOP fibrotic lesions in CBA/J mice and suggests that T(H)1-derived cytokines, especially IFN-gamma, may play a key role in fibrotic lesion development.