Role of T cell subsets in the development of AIDS-associated interstitial pneumonitis in mice.
Role of T cell subsets in the development of AIDS-associated interstitial pneumonitis in mice.
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T 细胞亚群在小鼠艾滋病相关间质性肺炎发展中的作用。
DOI：
10.1080/019021499269990
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发表时间：
1999
影响因子：
1.7
通讯作者：
Cohen,DA
中科院分区：
文献类型：
--
作者：
Fitzpatrick,EA;Avdiushko,M;Kaplan,AM;Cohen,DA
特发性间质性肺炎（IP）是人类免疫缺陷病毒（HIV）感染的主要非感染性并发症，其特征为肺淋巴细胞浸润和肺功能障碍。使用逆转录病毒相关IP的鼠模型分析了CD 4+和CD 8 + T细胞群和INF-γ在IP发展中的作用。CD 8 + T细胞耗竭的感染小鼠与未治疗的感染小鼠类似地发展IP，表明CD 8 + T细胞群在IP中不起作用。此外，CD 8 + T细胞的耗竭并没有改变肺中病毒RNA的水平，这表明细胞毒性T细胞可能在控制肺中的病毒负荷方面没有作用。相反，感染小鼠中CD 4 + T细胞的耗竭阻止了IP的发展并抑制了炎性细胞因子的表达，表明CD 4 + T细胞对IP的发展很重要。用病毒感染10周的IFN-γ-/-小鼠出现IP，尽管与感染的野生型小鼠相比，淋巴细胞浸润的严重程度显著降低。数据表明，肺中持续存在的病毒抗原可能驱动CD 4 + T细胞介导的免疫应答，导致IFN-γ的慢性产生，其放大肺中的慢性炎症应答，导致组织损伤。
Idiopathic interstitial pneumonitis (IP), characterized by lymphocytic infiltration of the lung and pulmonary dysfunction, is a major noninfectious complication of human immunodeficiency virus (HIV) infection. The role of the CD4+ and CD8+ T cell populations and INF-gamma in the development of IP were analyzed using a murine model of retroviral-associated IP. Infected mice depleted of CD8+ T cells developed IP similarly to untreated infected mice, suggesting that the CD8+ T cell population does not play a role in IP. Furthermore, depletion of CD8+ T cells did not alter the level of viral RNA in lungs, suggesting that cytotoxic T cells may not serve a role in controlling virus burden in lungs. In contrast, depletion of CD4+ T cells in infected mice prevented the development of IP and inhibited inflammatory cytokine expression, suggesting that CD4+ T cells are important for the development of IP. IFN-gamma -/- mice infected with virus for 10 weeks developed IP, although the severity of lymphocytic infiltration was substantially reduced compared to infected wild-type mice. The data suggest that persistent viral antigen in the lung may drive a CD4+ T cell-mediated immune response, resulting in the chronic production of IFN-gamma which amplifies a chronic inflammatory response in the lung resulting in tissue injury.