Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/78013
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Type: Journal article
Title: Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines
Author: Hodge, G.
Hodge, S.
Holmes-Liew, C.
Reynolds, P.
Holmes, M.
Citation: Journal of Heart and Lung Transplantation, 2012; 31(8):888-895
Publisher: Elsevier Science Inc
Issue Date: 2012
ISSN: 1053-2498
1557-3117
Statement of
Responsibility: 
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N. Reynolds, Mark Holmes
Abstract: <h4>Background</h4>We previously showed that bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T-cell pro-inflammatory cytokines and granzyme B. We recently showed that natural killer (NK) T (NKT)-like cells are a major source of pro-inflammatory cytokines and granzymes in the blood of stable lung transplant patients. NK cells also produce these pro-inflammatory mediators, and we hypothesized that BOS may be associated with lack of immunosuppression of these pro-inflammatory mediators in NK and NKT-like cells.<h4>Method</h4>Granzyme, perforin, and intracellular cytokine profiles from stable transplant recipients, patients with evidence of BOS, and healthy controls were determined using multiparameter flow cytometry.<h4>Results</h4>The percentage of NK cells expressing granzymes and perforin was significantly increased in BOS patients compared with stable patients and in stable patients compared with controls (89% ± 13%, 69% ± 12%, 33% ± 14% for NK and 35% ± 19%, 12% ± 15%, and 2% ± 3% for NKT-like granzyme B producing cells for BOS, stable patients and controls, respectively). There was an increase in the percentage of NK and NKT-like cells producing interferon (IFN)-γ and tumor necrosis factor (TNF)-α in BOS compared with stable patients (36% ± 16% and 10% ± 4% for NK and 32% ± 13% and 17% ± 8% for NKT-like IFN-γ producing cells for BOS and stable patients, respectively). There was a significant correlation between increased NK IFN-γ and TNF-α and values of forced expiratory volume in 1 second.<h4>Conclusions</h4>BOS is associated with increased peripheral blood NK and NKT-like cells expressing granzymes, perforin, and Th1 pro-inflammatory cytokines. These cells may migrate to the lungs and have an impact in airway damage in BOS. Therapeutic targeting of these pro-inflammatory mediators and monitoring response longitudinally using this assay may reduce BOS.
Keywords: lung transplant
NKT-like cells
granzymes
IFN-γ
TNF-α
Rights: Crown copyright © 2012 Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.healun.2012.04.007
Grant ID: NHMRC
Published version: http://dx.doi.org/10.1016/j.healun.2012.04.007
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