BOS is associated with increased cytotoxic proinflammatory CD8 T, NKT-like, and NK cells in the small airways

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dc.contributor.authorHodge, G.
dc.contributor.authorHodge, S.
dc.contributor.authorYeo, A.
dc.contributor.authorNguyen, P.
dc.contributor.authorHopkins, E.
dc.contributor.authorHolmes-Liew, C.
dc.contributor.authorReynolds, P.
dc.contributor.authorHolmes, M.
dc.date.issued2017
dc.description.abstractBackground. Immunosuppression therapy after lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and proinflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in proinflammatory lymphocytes after transplant. It is unknown whether these proinflammatory lymphocytes target the small and/or large airways in BOS. Methods. Blood, bronchoalveolar lavage, large proximal, and small distal airway brushings were collected from patients with BOS (n = 10), stable lung transplant patients (n = 18), and healthy aged-matched controls (n = 10). Intracellular cytotoxic mediators (perforin/granzyme B), proinflammatory cytokines (IFNγ/TNFα), and expression of GCR were determined in lymphocytes subsets from cultured blood using flow cytometry. Results. Increases in CD8 Tcells, NKT-like cells, and NK cells were found in the small distal airways in BOS compared with stable patients and controls. An increase in perforin, granzyme B, IFNγ, TNFα, and a loss of GCR from these lymphocyte subsets was also found in BOS. GCR expression by CD8+ T cells from small airways correlated with FEV1 (R = 0.834, P = 0.039). Many of these changes significantly differed from those in the large airways. Conclusions. BOS is associated with increased cytotoxic/ proinflammatory CD8+ T, NKT-like, and NK cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve graft survival.
dc.description.statementofresponsibilityGreg Hodge, Sandra Hodge, Aeneas Yeo, Phan Nguyen, Emily Hopkins, Chien-Li Holmes-Liew, Paul N. Reynolds, and Mark Holmes
dc.identifier.citationTransplantation, 2017; 101(10):2469-2476
dc.identifier.doi10.1097/TP.0000000000001592
dc.identifier.issn0041-1337
dc.identifier.issn1440-1843
dc.identifier.orcidHodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]
dc.identifier.orcidNguyen, P. [0000-0002-8573-3574]
dc.identifier.orcidReynolds, P. [0000-0002-2273-1774]
dc.identifier.urihttp://hdl.handle.net/2440/110478
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.rightsCopyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1097/tp.0000000000001592
dc.titleBOS is associated with increased cytotoxic proinflammatory CD8 T, NKT-like, and NK cells in the small airways
dc.typeJournal article
pubs.publication-statusPublished

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