T Regulatory Cells in Stable Posttransplant Bronchiolitis Obliterans Syndrome

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Abstract
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.