Karolinska Institutet, Dept of Medicine, Lung Research Laboratory, L4: 01, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden.
Eur Respir J. 2012 Jul;40(1):110-21. doi: 10.1183/09031936.00166110. Epub 2011 Dec 19.
Sarcoidosis is a granulomatous disease of unknown aetiology, mainly affecting the lungs. Recently, T-cell responses towards a specific mycobacterial protein, catalase-peroxidase (mKatG), were observed in sarcoidosis patients. Bronchoalveolar lavage (BAL) fluid and peripheral blood were obtained from a total of 23 sarcoidosis patients, of whom 13 had Löfgren's syndrome and lung accumulations of T-cell receptor AV2S3+ T-cells. Using six-colour flow cytometry in combination with intracellular cytokine staining, T-cell subsets were studied with regard to interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin-2 production, after stimulation with mKatG or Mycobacterium tuberculosis purified protein derivate (PPD). Stimulation with mKatG resulted in higher simultaneous IFN-γ and TNF production, but less single IFN-γ production, from total BAL fluid CD4+ T-cells of Löfgren's syndrome patients, when compared with non-Löfgren's patients. In contrast, PPD stimulation gave rise to largely similar cytokine responses in both patient subgroups. Furthermore, mKatG stimulated higher IFN-γ production in BAL fluid and blood AV2S3+ T-cells than AV2S3- T-cells, whereas the opposite was seen in BAL fluid with PPD stimulation. Our finding that patients with Löfgren's syndrome exhibited a more pronounced multifunctional cytokine profile (simultaneous IFN-γ and TNF production) towards the mycobacterial protein mKatG may help to explain the distinct disease presentation in this patient subgroup.
结节病是一种病因不明的肉芽肿性疾病，主要影响肺部。最近，在结节病患者中观察到针对一种特定的分枝杆菌蛋白，即过氧化氢酶-过氧化物酶（mKatG）的 T 细胞反应。共从 23 名结节病患者中获得支气管肺泡灌洗液（BAL）和外周血，其中 13 名患有 Löfgren 综合征和 T 细胞受体 AV2S3+T 细胞的肺部积聚。使用六色流式细胞术结合细胞内细胞因子染色，研究了 mKatG 或结核分枝杆菌纯化蛋白衍生物（PPD）刺激后 T 细胞亚群的 IFN-γ、肿瘤坏死因子（TNF）和白细胞介素-2 产生情况。与非 Löfgren 患者相比，Löfgren 综合征患者的总 BAL 液 CD4+T 细胞对 mKatG 的刺激导致同时产生更高水平的 IFN-γ 和 TNF，但单产 IFN-γ 水平较低。相比之下，PPD 刺激在两个患者亚组中均引起相似的细胞因子反应。此外，mKatG 刺激 BAL 液和血液 AV2S3+T 细胞产生的 IFN-γ 高于 AV2S3-T 细胞，而 PPD 刺激则相反。我们发现 Löfgren 综合征患者对分枝杆菌蛋白 mKatG 表现出更明显的多功能细胞因子谱（同时产生 IFN-γ 和 TNF），这可能有助于解释该患者亚组中独特的疾病表现。
