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

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dc.contributor.authorHodge, G.
dc.contributor.authorHodge, S.
dc.contributor.authorHolmes-Liew, C.
dc.contributor.authorReynolds, P.
dc.contributor.authorHolmes, M.
dc.date.issued2012
dc.description.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.
dc.description.statementofresponsibilityGreg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N. Reynolds, Mark Holmes
dc.identifier.citationJournal of Heart and Lung Transplantation, 2012; 31(8):888-895
dc.identifier.doi10.1016/j.healun.2012.04.007
dc.identifier.issn1053-2498
dc.identifier.issn1557-3117
dc.identifier.orcidHodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]
dc.identifier.orcidReynolds, P. [0000-0002-2273-1774]
dc.identifier.urihttp://hdl.handle.net/2440/78013
dc.language.isoen
dc.publisherElsevier Science Inc
dc.relation.grantNHMRC
dc.rightsCrown copyright © 2012 Published by Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.healun.2012.04.007
dc.subjectlung transplant
dc.subjectNKT-like cells
dc.subjectgranzymes
dc.subjectIFN-γ
dc.subjectTNF-α
dc.titleBronchiolitis 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
dc.typeJournal article
pubs.publication-statusPublished

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