SELECTIVE ACTIVATION AND ACCUMULATION OF OLIGOCLONAL V-BETA-SPECIFIC T-CELLS IN ACTIVE PULMONARY SARCOIDOSIS
SELECTIVE ACTIVATION AND ACCUMULATION OF OLIGOCLONAL V-BETA-SPECIFIC T-CELLS IN ACTIVE PULMONARY SARCOIDOSIS
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DOI：
10.1172/jci117494
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发表时间：
1994-10-01
影响因子：
15.9
通讯作者：
MOLLER, DR
中科院分区：
文献类型：
--
作者：
FORMAN, JD;KLEIN, JT;MOLLER, DR
结节病是一种肉芽肿性疾病，在这种疾病中，激活的T细胞对一种未知的刺激作出反应，在疾病部位（如肺）积聚。为了评估活动性结节病以选择性激活和扩增有限的T细胞受体（TCR）特异性T细胞为特征的假设，我们分析了活动性结节病患者肺和血液T细胞中的TCR V β基因表达，并使用20 V β基因家族的聚合酶链反应扩增正常人。对正常支气管肺泡灌洗T细胞的分析显示，TCR V β分布与正常血液相似，这为正常、未感染肺中T细胞库缺乏普遍偏态提供了证据。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V β基因的偏表达。5个V β基因家族（V β 5、V β 8、V β 15、V β 16和V β 18）最常被结节肺或血液T细胞以偏倚的方式利用。此外，当肺肉瘤和血液T细胞通过IL-2短期培养扩增时，T细胞库明显倾斜。序列分析表明，V β基因表达的偏倚通常是由于选择V β特异性克隆的扩增，其中一些克隆含有类似的V(D)J连接区基序。这些观察结果为结节病中抗原特异性V β表达T细胞的选择性激活和积累提供了证据。
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.