Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome.
BACKGROUND
Lung transplantation, in patients with end-stage lung disease, is limited by chronic rejection, which occurs with an incidence and severity exceeding most other transplanted organs. Alloimmune responses play an important role in progression to chronic rejection that manifests as bronchiolitis obliterans syndrome (BOS), but no biomarker can currently predict the progression to BOS. Studies in animal models suggest that intragraft T regulatory cells (Tregs) are important in maintaining transplantation tolerance, and FoxP3 is the protoypic Treg marker.


METHODS
Leukocytes in blood and bronchoalveolar lavage (BAL) fluid were compared for expression of FoxP3 by flow cytometry in 14 stable lung transplant recipients and 6 lung transplant recipients who eventually developed BOS.


RESULTS
Stable patients, compared with patients who subsequently developed BOS, consistently had a significantly increased percentage of FoxP3 cells among CD4 cells in BAL and greater levels of the Treg-attracting chemokine CCL22. These differences were observed in limited sequential analyses, before, at the time of acute rejection, and postacute rejection. In this pilot study, a threshold of 3.2% CD4/FoxP3 cells in the BAL distinguished stable recipients from those subsequently developing BOS within the first 2 years posttransplantation.


CONCLUSIONS
The proportion of FoxP3 cells among CD4 cells in BAL may help to predict lung allograft outcome and guide therapeutic immunosuppression in lung transplant recipients.
Bhorade
Sangeeta M
SM
Section of Pulmonary, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. sbhorade@medicine.bsd.uchicago.edu
Chen
Hong
H
Molinero
Luciana
L
Liao
Chuanhong
C
Garrity
Edward R
ER
Vigneswaran
Wickii T
WT
Shilling
Rebecca
R
Sperling
Anne
A
Chong
Anita
A
Alegre
Maria-Luisa
ML
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery; D012372:ROC Curve; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology; D055815:Young Adult