Wahlström Jan, Dengjel Jörn, Winqvist Ola, Targoff Ira, Persson Bengt, Duyar Hüseyin, Rammensee Hans-Georg, Eklund Anders, Weissert Robert, Grunewald Johan
Karolinska Institutet, Department of Medicine, Lung Research Laboratory, L4:01, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden.
Clin Immunol. 2009 Dec;133(3):353-63. doi: 10.1016/j.clim.2009.08.008. Epub 2009 Sep 27.
The etiology of sarcoidosis remains unknown. Recently, by mass spectrometric sequencing of peptides eluted from HLA-DR molecules of bronchoalveolar lavage (BAL) cells from DRB10301(pos) patients, we identified potential self-antigens in sarcoidosis. The aim of the present study was to investigate the capacity of selected peptides to stimulate lung and blood T cells of sarcoidosis patients using an interferon-gamma ELISPOT assay. In peripheral blood, there were strong T cell responses to a peptide derived from the cytoskeletal protein vimentin in 6 out of 11 DRB10301(pos) patients with active disease but not in patients with other HLA types. BAL T cell responses against peptides derived from ATP synthase or from lysyl-tRNA synthetase were detected in DRB10301(pos) as well as DRB10301(neg) patients. By using antigenic peptides presented in vivo in the lungs of sarcoidosis patients, we have identified blood and lung T cell autoimmune responses that may help sustain the inflammation in this disease.
结节病的病因仍然不明。最近,通过对来自DRB10301阳性患者支气管肺泡灌洗(BAL)细胞的HLA-DR分子洗脱的肽段进行质谱测序,我们在结节病中鉴定出了潜在的自身抗原。本研究的目的是使用干扰素-γ ELISPOT试验研究选定肽段刺激结节病患者肺和血液T细胞的能力。在11例患有活动性疾病的DRB10301阳性患者中,有6例患者的外周血对源自细胞骨架蛋白波形蛋白的肽段有强烈的T细胞反应,而其他HLA类型的患者则没有。在DRB10301阳性以及DRB10301阴性患者中均检测到BAL T细胞对源自ATP合酶或赖氨酰-tRNA合成酶的肽段的反应。通过使用结节病患者肺内体内呈现的抗原肽段,我们已经鉴定出可能有助于维持该疾病炎症的血液和肺T细胞自身免疫反应。