Hodge, G.Hodge, S.Holmes-Liew, C.Reynolds, P.Holmes, M.2013-05-272013-05-272012Journal of Heart and Lung Transplantation, 2012; 31(8):888-8951053-24981557-3117http://hdl.handle.net/2440/78013<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.enCrown copyright © 2012 Published by Elsevier Inc. All rights reserved.lung transplantNKT-like cellsgranzymesIFN-γTNF-αJournal article002012765910.1016/j.healun.2012.04.0070003064490000152-s2.0-8486332037920044Hodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]Reynolds, P. [0000-0002-2273-1774]