Forman J D, Klein J T, Silver R F, Liu M C, Greenlee B M, Moller D R
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Clin Invest. 1994 Oct;94(4):1533-42. doi: 10.1172/JCI117494.
Sarcoidosis is a granulomatous disease in which activated T cells, responding to an unidentified stimulus, accumulate at sites of disease such as the lung. To evaluate the hypothesis that active sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR) specific T cells, we analyzed TCR V beta gene expression in lung and blood T cells of patients with active sarcoidosis and, for comparison, normal individuals using polymerase chain reaction amplification of 20 V beta gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR V beta distributions similar to that of normal blood, providing evidence for a lack of generalized skewing of the T cell repertoire in the normal, noninfected lung. Compared to normal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more V beta genes in either the lung or blood. Five V beta gene families (V beta 5, V beta 8, V beta 15, V beta 16, and V beta 18) were most frequently utilized in a biased fashion by sarcoid lung or blood T cells. Furthermore, dramatic skewing of the T cell repertoire was apparent when sarcoid lung and blood T cells were expanded by short-term culture with IL-2. Sequence analysis demonstrated a bias in V beta gene expression was usually due to expansion of select V beta-specific clones, some of which contained a similar V(D)J junctional region motif. These observations provide evidence for a selective activation and accumulation of antigen-specific V beta-expressing T cells in sarcoidosis.
结节病是一种肉芽肿性疾病，其中活化的T细胞对未知刺激作出反应，在肺部等疾病部位聚集。为了评估活动性结节病的特征是有限的T细胞受体（TCR）特异性T细胞库的选择性激活和扩增这一假说，我们使用聚合酶链反应扩增20个Vβ基因家族，分析了活动性结节病患者及作为对照的正常个体的肺和血液T细胞中的TCR Vβ基因表达。对正常支气管肺泡灌洗T细胞的分析显示，其TCR Vβ分布与正常血液相似，这为正常未感染肺中T细胞库缺乏普遍偏斜提供了证据。与正常肺和血液相比，结节病患者亚组在肺或血液中表现出一个或多个Vβ基因的偏向性表达。五个Vβ基因家族（Vβ5、Vβ8、Vβ15、Vβ16和Vβ18）最常被结节病肺或血液T细胞以偏向性方式利用。此外，当结节病肺和血液T细胞用IL-2进行短期培养扩增时，T细胞库的显著偏斜很明显。序列分析表明，Vβ基因表达的偏向通常是由于特定Vβ特异性克隆的扩增，其中一些克隆包含相似的V（D）J连接区基序。这些观察结果为结节病中抗原特异性Vβ表达T细胞的选择性激活和积累提供了证据。
