T regulatory cells in stable posttransplant bronchiolitis obliterans syndrome.
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.


CONCLUSIONS
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.
Mamessier
Emilie
E
UPRES 3287, IPHM IFR125, Faculté de Médecine, Université de Méditerranée, Marseille, France.
Lorec
Anne-Marie
AM
Thomas
Pascal
P
Badier
Monique
M
Magnan
Antoine
A
Reynaud-Gaubert
Martine
M
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011183:Postoperative Complications; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens