Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/110478
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Type: Journal article
Title: BOS is associated with increased cytotoxic proinflammatory CD8 T, NKT-like, and NK cells in the small airways
Author: Hodge, G.
Hodge, S.
Yeo, A.
Nguyen, P.
Hopkins, E.
Holmes-Liew, C.
Reynolds, P.
Holmes, M.
Citation: Transplantation, 2017; 101(10):2469-2476
Publisher: Lippincott Williams & Wilkins
Issue Date: 2017
ISSN: 0041-1337
1440-1843
Statement of
Responsibility: 
Greg Hodge, Sandra Hodge, Aeneas Yeo, Phan Nguyen, Emily Hopkins, Chien-Li Holmes-Liew, Paul N. Reynolds, and Mark Holmes
Abstract: Background. 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.
Rights: Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/TP.0000000000001592
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