{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:38:24Z","timestamp":1762875504481,"version":"3.37.3"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,6,6]],"date-time":"2013-06-06T00:00:00Z","timestamp":1370476800000},"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\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T cell proinflammatory cytokines and increased T cell granzyme B. Repeated antigen-driven proliferation down-regulates T cell CD28. We hypothesized that down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules (CD134, CD137, CD152 and CD154) on T cells may be associated with BOS. Co-stimulatory molecules, granzyme B, perforin and intracellular cytokines were measured by flow cytometry on T cells from stable lung transplant patients (n\u2009=\u200938), patients with BOS (n\u2009=\u200920) and healthy controls (n\u2009=\u200910). There was a significant increase in the percentage of CD4\/28null and CD8\/28null T cells producing granzyme B, interferon (IFN)-\u03b3 and tumour necrosis factor (TNF)-\u03b1 in BOS compared with stable patients. Down-regulation of CD28 was associated with steroid resistance and up-regulation of CD134, CD137, CD152 and CD154 on CD4+ T cells and CD137 and CD152 on CD8+ T cells. There was a significant correlation between increased CD28null\/CD137 T cells producing IFN-\u03b3, TNF-\u03b1 with BOS grade (r\u2009=\u20090\u00b7861, P\u2009&amp;lt;\u20090\u00b7001 for CD28null\/CD137 IFN-\u03b3\/CD8) and time post-transplant (r\u2009=\u20090\u00b7698, P\u2009&amp;lt;\u20090\u00b7001 for CD28null\/CD137 IFN-\u03b3\/CD8). BOS is associated with down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules on steroid-resistant peripheral blood proinflammatory CD4+ and CD8+ T cells. Therapeutic targeting of alternate co-stimulatory molecules on peripheral blood CD28null T cells and monitoring response using these assays may help in the management of patients with BOS.<\/jats:p>","DOI":"10.1111\/cei.12081","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T11:56:55Z","timestamp":1359460615000},"page":"150-160","source":"Crossref","is-referenced-by-count":12,"title":["Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome"],"prefix":"10.1093","volume":"173","author":[{"given":"G","family":"Hodge","sequence":"first","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Hodge","sequence":"additional","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Ahern","sequence":"additional","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C-L","family":"Holmes-Liew","sequence":"additional","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"},{"name":"South Australian Lung Transplant Service, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P N","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Holmes","sequence":"additional","affiliation":[{"name":"Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia"},{"name":"University of Adelaide, Adelaide, SA, Australia"},{"name":"South Australian Lung Transplant Service, Adelaide, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,6,6]]},"reference":[{"key":"2021122009553872600_cei12081-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 beyond 5 years","volume":"37","author":"Lama","year":"2005","journal-title":"Transplant 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