Hodge, G.Hodge, S.Yeo, A.Nguyen, P.Hopkins, E.Holmes-Liew, C.Reynolds, P.Holmes, M.2018-02-072018-02-072017Transplantation, 2017; 101(10):2469-24760041-13371440-1843http://hdl.handle.net/2440/110478Background. 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.enCopyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.Journal article003004879510.1097/TP.00000000000015922-s2.0-85000948415245068Hodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]Nguyen, P. [0000-0002-8573-3574]Reynolds, P. [0000-0002-2273-1774]