Möllers M, Aries S P, Drömann D, Mascher B, Braun J, Dalhoff K
Department of Medicine II, Medical University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Thorax. 2001 Jun;56(6):487-93. doi: 10.1136/thorax.56.6.487.
Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry.
Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease.
Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells.
Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.
肺结节病的特征是单核细胞性肺泡炎,以CD4+ T细胞和巨噬细胞为主。我们使用三色流式细胞术测定了血液和支气管肺泡灌洗(BAL)液中CD4+和CD8+、初始和记忆淋巴细胞内干扰素(IFN)γ、白细胞介素(IL)-2、肿瘤坏死因子(TNF)α、IL-4、IL-5和IL-10的表达。
对18例未经治疗的肺结节病患者进行评估,并根据其患有急性或慢性疾病进行分层。
无论临床表现如何,在BAL液和外周血样本中,表达Th1型细胞因子的T细胞均显著多于表达Th2型细胞因子的T细胞。BAL液中分泌Th1型细胞因子的T细胞比例显著高于外周血。与慢性疾病相比,急性疾病中外周血和肺泡T细胞更频繁地表达Th1型细胞因子。CD4+和CD8+ T细胞之间无显著差异。关于初始和记忆淋巴细胞,BAL液中的CD45RO:CD45RA比值显著高于血液,与肺泡记忆T细胞相比,外周血记忆T细胞中Th2型细胞因子的表达增加。
我们的数据支持肺结节病中Th1/Th2失衡和分隔的免疫发病机制概念,并表明细胞因子模式在疾病过程中发生变化。与外周血相比,肺泡腔中记忆淋巴细胞内Th2型细胞因子的表达降低。