Mamessier Emilie, Lorec Anne-Marie, Thomas Pascal, Badier Monique, Magnan Antoine, Reynaud-Gaubert Martine
UPRES 3287, IPHM IFR125, Faculté de Médecine, Université de Méditerranée, Marseille, France.
Transplantation. 2007 Oct 15;84(7):908-16. doi: 10.1097/01.tp.0000281408.20686.cb.
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).
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).
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.
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.
闭塞性细支气管炎（OB）主要由T细胞介导，仍然是长期肺移植中发病和死亡的主要原因。急性排斥反应（AR）也是一个由T细胞介导的过程，与OB密切相关。出于未知原因，一些患有OB的患者停止了肺功能下降，并在很长一段时间内稳定了其阻塞性缺陷。我们的目的是评估急性排斥反应（AR）、稳定期OB（sOB）和进展期OB（eOB）期间血液、诱导痰和支气管肺泡灌洗中的T细胞活化情况。
通过流式细胞术评估这三个部位的T细胞表型和细胞因子产生情况。通过酶联免疫吸附测定法测量血细胞培养上清液中的白细胞介素-4、干扰素-γ和转化生长因子（TGF）-β水平。将健康肺移植受者与AR（n = 7）、sOB（n = 7）和eOB（n = 13）的结果进行比较。
稳定期和进展期OB的特征是调节性T细胞（Treg）、辅助性T细胞1（Th1）和辅助性T细胞2（Th2）活化，但与eOB相比，Treg和Th2细胞在sOB中占主导地位。在AR中观察到明显的Th1活化。TGF-β在AR和进展期OB中升高。
这些初步结果表明，根据临床情况，T细胞活化情况存在差异。我们推测Treg细胞可以抵消进展期OB中出现的初始T细胞（Th0）活化，并参与气道阻塞的稳定。
