Trentin L, Zambello R, Facco M, Tassinari C, Sancetta R, Siviero M, Cerutti A, Cipriani A, Marcer G, Majori M, Pesci A, Agostini C, Semenzato G
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Italy.
Am J Respir Crit Care Med. 1997 Feb;155(2):587-96. doi: 10.1164/ajrccm.155.2.9032199.
Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can be activated in vitro through the TCR, blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE. Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments were overrepresented in the lung rather than in the blood. Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the recovery of the alveolitis was characterized by the disappearance of cells bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to different superantigens demonstrated that the proliferation elicited by different staphylococcal toxins was more pronounced in the lung than in the blood. Taken together, our findings indicate a compartmentalization of cells bearing discrete Vbeta gene products in the pulmonary microenvironment and suggest that the expansion of specific Vbeta region subsets occurring in the lung might result from triggering by a specific antigen. In fact, the removal from exposure in HP patients or specific treatment in sarcoidosis resulted in the decrease of the overrepresented cell population accounting for the lymphocytic alveolitis.
过敏性肺炎（HP）和结节病是间质性肺疾病（ILD），其特征为淋巴细胞性肺泡炎，在疾病的活动期，由不同的T细胞亚群维持，即HP中的CD8 +细胞和结节病患者中的CD4 +淋巴细胞。为了解决HP和结节病患者肺部是否存在T细胞选择偏差的问题，我们通过流式细胞术和聚合酶链反应（PCR）分析，对14例HP患者和25例结节病患者的血液和肺淋巴细胞中的T细胞受体β链可变区（TCR-Vβ）库进行了分析。为了验证这些细胞是否能通过TCR在体外被激活，还评估了血液和肺淋巴细胞对由葡萄球菌肠毒素代表的不同超抗原刺激的反应性，包括SEA、SEB、SEC1、SEC2、SED和SEE。流式细胞术和PCR分析表明，与外周血相比，HP患者肺部携带Vβ2、Vβ3、Vβ5、Vβ6和Vβ8基因片段的细胞过度表达。在结节病患者中，与外周血相比，HP患者肺部携带Vβ2、Vβ5和Vβ6基因片段的细胞过度表达。在结节病患者中，携带Vβ2、Vβ5和Vβ6基因片段的细胞在肺部而非血液中占优势。在HP和结节病患者中，几乎所有携带显性Vβ片段的T细胞都属于维持肺泡炎的T细胞亚群，即HP患者中的CD8和结节病患者中的CD4。随访研究表明，肺泡炎的恢复以具有有限T细胞库的细胞消失为特征。有趣的是，T淋巴细胞对不同超抗原的反应表明，不同葡萄球菌毒素引发的增殖在肺部比在血液中更明显。综上所述，我们的研究结果表明在肺微环境中携带离散Vβ基因产物的细胞存在分隔，并表明肺部发生的特定Vβ区域亚群的扩增可能是由特定抗原触发的。事实上，HP患者脱离暴露或结节病患者接受特定治疗后，导致占淋巴细胞性肺泡炎的过度表达细胞群体减少。
