Fitzpatrick E A, Avdiushko M, Kaplan A M, Cohen D A
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0084, USA.
Exp Lung Res. 1999 Dec;25(8):671-87. doi: 10.1080/019021499269990.
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.
特发性间质性肺炎（IP）以肺部淋巴细胞浸润和肺功能障碍为特征，是人类免疫缺陷病毒（HIV）感染的主要非感染性并发症。使用逆转录病毒相关IP的小鼠模型分析了CD4 +和CD8 + T细胞群体以及INF-γ在IP发生发展中的作用。耗尽CD8 + T细胞的感染小鼠与未治疗的感染小鼠一样发生IP，这表明CD8 + T细胞群体在IP中不起作用。此外，耗尽CD8 + T细胞不会改变肺中病毒RNA的水平，这表明细胞毒性T细胞可能在控制肺中病毒载量方面不起作用。相比之下，感染小鼠中CD4 + T细胞的耗尽可预防IP的发生并抑制炎性细胞因子的表达，这表明CD4 + T细胞对IP的发生发展很重要。感染病毒10周的IFN-γ-/-小鼠发生了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大大降低。数据表明，肺中持续存在的病毒抗原可能驱动CD4 + T细胞介导的免疫反应，导致IFN-γ的慢性产生，从而放大肺中的慢性炎症反应，导致组织损伤。
