{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:31:23Z","timestamp":1771273883796,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001786","name":"University of Adelaide","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal Adelaide Hospital Brine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We previously showed increased steroid-resistant CD28null CD8+ senescent lymphocyte subsets in the peripheral blood from patients with chronic obstructive pulmonary disease (COPD). These cells expressed decreased levels of the glucocorticoid receptor (GCR), suggesting their contribution to the steroid-resistant property of these cells. COPD is a disease of the small airways (SA). We, therefore, hypothesized that there would be a further increase in these steroid-resistant lymphocytes in the lung, particularly in the SA. We further hypothesized that the pro-inflammatory\/cytotoxic potential of these cells could be negated using prednisolone with low-dose cyclosporin A. Blood, bronchoalveolar lavage, large proximal, and small distal airway brushings were collected from 11 patients with COPD and 10 healthy aged-matched controls. The cytotoxic mediator granzyme b, pro-inflammatory cytokines IFN\u03b3\/TNF\u03b1, and GCR were determined in lymphocytes subsets before and after their exposure to 1\u00b5M prednisolone and\/or 2.5\u00a0ng\/mL cyclosporin A. Particularly in the SA, COPD subjects showed an increased percentage of CD28null CD8 T-cells and NKT-like cells, with increased expression of granzyme b, IFN\u03b3 and TNF\u03b1 and a loss of GCR, compared with controls. Significant negative correlations between SA GCR expression and IFN\u03b3\/TNF\u03b1 production by T and NKT-like cells (eg, T-cell IFN\u03b3 R = \u22120.834, P = 0.031) and with FEV1 (R = \u22120.890) were shown. Cyclosporine A and prednisolone synergistically increased GCR expression and inhibited pro-inflammatory cytokine production by CD28null CD8\u2212 T and NKT-like cells. COPD is associated with increased pro-inflammatory CD28null CD8+ T and NKT-like cells in the SA. Treatments that increase GCR in these lymphocyte subsets may improve the efficacy of clinical treatment.<\/jats:p>","DOI":"10.1093\/cei\/uxab037","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T18:57:06Z","timestamp":1641236226000},"page":"351-359","source":"Crossref","is-referenced-by-count":14,"title":["COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8689-963X","authenticated-orcid":false,"given":"Greg","family":"Hodge","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubertus","family":"Jersmann","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai B","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick F","family":"Asare","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minnu","family":"Jayapal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul N","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Hodge","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SouthAustralia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, SouthAustralia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"2022051714134742200_CIT0001","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1183\/09031936.03.00040703","article-title":"Chronic obstructive 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