{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T20:59:02Z","timestamp":1762376342862,"version":"3.37.3"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T00:00:00Z","timestamp":1518566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Respiratory Clinical Trials Unit"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,18]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Immunosuppressive therapy fails to suppress the production of proinflammatory cytokines, particularly by CD8+ T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant. Pgp\/GCR expression and interferon (IFN)-\u03b3\/tumour necrosis factor (TNF)-\u03b1 proinflammatory cytokine production was measured in blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (\u00b1\u00a0prednisolone\u00a0\u00b1\u00a0Pgp inhibitor, cyclosporin A\u00a0\u00b1\u00a0GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp\u2013 lymphocyte subsets from all subjects produced IFN-\u03b3\/TNF-\u03b1 proinflammatory cytokines. Pgp expression was increased in CD8+Pgp+ T cells and correlated with IFN-\u03b3\/TNF-\u03b1 expression and BOS grade. Reduced GCR was observed in CD8+Pgp\u2013 T, natural killer (NK)\u00a0T-like and NK cells from stable patients compared with controls, and reduced further in CD8+Pgp\u2013 T cells in BOS. The addition of 2\u00b75\u00a0ng\/ml cyclosporin A and 1\u00a0\u00b5M prednisolone inhibit IFN-\u03b3\/TNF-\u03b1 production significantly by CD8+Pgp+ T cells from BOS patients. The addition of 10\u00a0\u00b5M Compound A and 1 \u00b5M prednisolone inhibit IFN-\u03b3\/TNF-\u03b1 production significantly by CD8+Pgp\u2013 T cells from BOS patients. BOS is associated with increased Pgp expression and loss of GCR from steroid-resistant proinflammatory CD8+ T cells. Treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells may improve graft survival.<\/jats:p>","DOI":"10.1111\/cei.13103","type":"journal-article","created":{"date-parts":[[2018,1,20]],"date-time":"2018-01-20T10:14:39Z","timestamp":1516443279000},"page":"242-250","source":"Crossref","is-referenced-by-count":6,"title":["Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein expression and loss of glucocorticoid receptor from steroid-resistant proinflammatory CD8+ T cells"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8689-963X","authenticated-orcid":false,"given":"G","family":"Hodge","sequence":"first","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Hodge","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P T","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Yeo","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Badiei","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C L","family":"Holmes-Liew","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"},{"name":"South Australian Lung Transplant Service, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P N","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Holmes","sequence":"additional","affiliation":[{"name":"Lung Research Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia"},{"name":"South Australian Lung Transplant Service, Adelaide, South Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,2,14]]},"reference":[{"key":"2021120808312796300_cei13103-bib-0001","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.transproceed.2005.02.032","article-title":"Analysis of lung transplant recipients surviving 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