Enelow R I, Mohammed A Z, Stoler M H, Liu A N, Young J S, Lou Y H, Braciale T J
The, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
J Clin Invest. 1998 Nov 1;102(9):1653-61. doi: 10.1172/JCI4174.
CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell infiltration that correlated with restrictive pulmonary mechanics and a progressive diffusion impairment. These results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.
在许多临床情况下，尤其是间质性肺疾病中，CD8(+) T细胞会浸润肺部。目前尚不清楚CD8(+) T细胞在炎症性肺疾病发病机制中可能发挥的作用，以及CD8(+) T细胞效应活动对肺损伤的直接影响。本报告描述了一种转基因模型，用于评估肺泡上皮细胞内源性表达的靶抗原被CD8(+) T淋巴细胞识别后对呼吸结构和功能的影响。我们发现，将针对肺泡新抗原（流感血凝素）的克隆CD8(+) 细胞毒性T淋巴细胞（CTL）过继转移到转基因小鼠中会导致进行性致命损伤，这对肺结构和功能产生了显著影响。接受CD8(+) CTL的转基因受体表现出呼吸急促和体重逐渐减轻，在几天内濒死。与此同时，这些动物发展为进行性间质性肺炎，最初表现为肺泡壁和肺泡腔的淋巴细胞浸润，随后是大量单核细胞浸润，这与限制性肺力学和进行性弥散障碍相关。这些结果表明，抗原特异性CD8(+) T细胞对肺泡上皮“自身抗原”的识别本身就足以引发炎症级联反应，导致间质性肺炎的组织学和生理学表现。
