Forrester J M, Newman L S, Wang Y, King T E, Kotzin B L
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J Clin Invest. 1993 Jan;91(1):292-300. doi: 10.1172/JCI116184.
Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for gamma/delta T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular gamma/delta T cell receptors. An abnormally high percentage of gamma/delta cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing alpha/beta receptors. Furthermore, as in normals, the circulating gamma/delta cells in patients predominantly expressed V gamma 9/V delta 2 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of gamma/delta cells expressing V delta 1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V delta 1+ cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus.
结节病是一种病因不明的多系统疾病，其特征是受累组织中存在非干酪样肉芽肿。为了研究γ/δT细胞在肺结节病发病机制中的潜在作用，我们研究了患者的肺和血液T细胞，以观察特定γ/δT细胞受体的优先表达情况。在一些患者的血液中发现γ/δ细胞的百分比异常高。然而，百分比的增加并不反映绝对数量的增加，似乎是由于表达α/β受体的T细胞减少所致。此外，与正常人一样，患者循环中的γ/δ细胞主要表达Vγ9/Vδ2受体，这一亚群在疾病部位并未富集。相反，在肺中，一部分患者中表达Vδ1的γ/δ细胞百分比增加。重要的是，这些细胞在白细胞介素2存在的情况下在体外选择性扩增，显示出先前激活的证据。此外，对连接区序列的分析揭示了它们的克隆性质。肺结节病中Vδ1+细胞的这些克隆扩增为一种疾病过程提供了证据，该过程涉及T细胞对局部抗原的特异性识别，并为尚未明确的抗原刺激的性质提供了新信息。
