BACKGROUND: Obliterative bronchiolitis (OB), mainly mediated by T cells, remains the major cause of morbidity and death in long-term lung transplant. Acute rejection (AR), also a T-cell mediated process, is strongly linked to OB. For unknown reasons, several patients with OB halt their pulmonary function decline and stabilize their obstructive defect for a long period. Our aim was to assess the T-cell activation in blood, induced sputum, and broncho-alveolar lavage during AR, stable OB (sOB), and evolving OB (eOB). METHODS: T-cell phenotype and cytokine production were assessed by flow cytometry in these three compartments. Interleukin-4, interferon-gamma and transforming growth factor (TGF)-beta levels were measured by enzyme-linked immunosorbent assay in blood cell culture supernatants. Results were compared between healthy lung transplant recipients and AR (n=7), sOB (n=7), and eOB (n=13). RESULTS: Stable and evolutive OB were characterized by a Treg, Th1, and Th2 activation, but compared to eOB, Treg and Th2 cells predominated in sOB. A clear Th1 activation was observed in AR. TGF-beta was increased in AR and evolving OB. CONCLUSION: These preliminary results indicate a contrasted T-cell activation profile depending on the clinical conditions. We speculate that Treg cells could counterbalance the Th0 activation seen in evolving OB and participate in stabilization of airway obstruction.
BACKGROUND: Obliterative bronchiolitis (OB), mainly mediated by T cells, remains the major cause of morbidity and death in long-term lung transplant. Acute rejection (AR), also a T-cell mediated process, is strongly linked to OB. For unknown reasons, several patients with OB halt their pulmonary function decline and stabilize their obstructive defect for a long period. Our aim was to assess the T-cell activation in blood, induced sputum, and broncho-alveolar lavage during AR, stable OB (sOB), and evolving OB (eOB). METHODS: T-cell phenotype and cytokine production were assessed by flow cytometry in these three compartments. Interleukin-4, interferon-gamma and transforming growth factor (TGF)-beta levels were measured by enzyme-linked immunosorbent assay in blood cell culture supernatants. Results were compared between healthy lung transplant recipients and AR (n=7), sOB (n=7), and eOB (n=13). RESULTS: Stable and evolutive OB were characterized by a Treg, Th1, and Th2 activation, but compared to eOB, Treg and Th2 cells predominated in sOB. A clear Th1 activation was observed in AR. TGF-beta was increased in AR and evolving OB. CONCLUSION: These preliminary results indicate a contrasted T-cell activation profile depending on the clinical conditions. We speculate that Treg cells could counterbalance the Th0 activation seen in evolving OB and participate in stabilization of airway obstruction.
Authors: Peter H Hagedorn; Christopher M Burton; Jørn Carlsen; Daniel Steinbrüchel; Claus B Andersen; Eli Sahar; Eytan Domany; Irun R Cohen; Henrik Flyvbjerg; Martin Iversen Journal: Immunology Date: 2010-02-26 Impact factor: 7.397
Authors: Yizhan Guo; Qing Wang; Dongge Li; Oscar Okwudiri Onyema; Zhongcheng Mei; Amir Manafi; Anirban Banerjee; Bayan Mahgoub; Mark H Stoler; Thomas H Barker; David S Wilkes; Andrew E Gelman; Daniel Kreisel; Alexander Sasha Krupnick Journal: Am J Transplant Date: 2019-08-02 Impact factor: 8.086
Authors: Elisabeth A Kastelijn; Coline Hm van Moorsel; Karin M Kazemier; Suzan M Roothaan; Henk Jt Ruven; Johanna M Kwakkel-van Erp; Ed A van de Graaf; Pieter Zanen; Diana A van Kessel; Jan C Grutters Journal: Fibrogenesis Tissue Repair Date: 2011-11-01