BOS is Associated with Increased Cytotoxic Pro-inflammatory CD8 T, NKT-like and NK Cells in the Small Airways.

BACKGROUND: Immunosuppression therapy following 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 pro-inflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in pro-inflammatory lymphocytes following transplant. It is unknown whether these pro-inflammatory 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), pro-inflammatory cytokines (IFN[gamma]/TNF[alpha]) and expression of GCR were determined in lymphocytes subsets from cultured blood using flow cytometry. RESULTS: Increases in CD8 T-cells, 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, IFN[gamma], TNF[alpha] 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=.834, p=.039). Many of these changes significantly differed from those in the large airways. CONCLUSIONS: BOS is associated with increased cytotoxic/pro-inflammatory CD8+ T, NKT-like and NK cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve graft survival. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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