T regulatory cells in stable posttransplant bronchiolitis obliterans syndrome

Transplantation. 2007 Oct 15;84(7):908-16. doi: 10.1097/01.tp.0000281408.20686.cb.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Bronchiolitis Obliterans / etiology
  • Bronchiolitis Obliterans / immunology*
  • CD3 Complex / biosynthesis
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lectins, C-Type
  • Lung Transplantation / adverse effects
  • Lung Transplantation / methods
  • Male
  • Middle Aged
  • Phenotype
  • Postoperative Complications
  • Syndrome
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Lectins, C-Type
  • Transforming Growth Factor beta
  • Interleukin-4
  • Interferon-gamma