{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:31:14Z","timestamp":1770348674966,"version":"3.49.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic beryllium disease (CBD) is an occupational lung disorder characterized by granulomatous inflammation and the accumulation of beryllium-responsive CD4+ T cells in the lung. These differentiated effector memory T cells secrete IL-2, IFN-\u03b3, and TNF-\u03b1 upon in vitro activation. Beryllium-responsive CD4+ T cells in the lung are CD28 independent and have increased expression of the coinhibitory receptor, programmed death 1, resulting in Ag-specific T cells that proliferate poorly yet retain the ability to express Th1-type cytokines. To further investigate the role of coinhibitory receptors in the beryllium-induced immune response, we examined the expression of CTLA-4 in blood and bronchoalveolar lavage cells from subjects with CBD. CTLA-4 expression was elevated on CD4+ T cells from the lungs of study subjects compared with blood. Furthermore, CTLA-4 expression was greatest in the beryllium-responsive subset of CD4+ T cells that retained the ability to proliferate and express IL-2. Functional assays show that the induction of CTLA-4 signaling in blood cells inhibited beryllium-induced T cell proliferation while having no effect on the proliferative capacity of beryllium-responsive CD4+ T cells in the lung. Collectively, our findings suggest a dysfunctional CTLA-4 pathway in the lung and its potential contribution to the persistent inflammatory response that characterizes CBD.<\/jats:p>","DOI":"10.4049\/jimmunol.1300282","type":"journal-article","created":{"date-parts":[[2013,7,13]],"date-time":"2013-07-13T05:40:13Z","timestamp":1373694013000},"page":"1648-1656","source":"Crossref","is-referenced-by-count":12,"title":["Impaired Function of CTLA-4 in the Lungs of Patients with Chronic Beryllium Disease Contributes to Persistent Inflammation"],"prefix":"10.1093","volume":"191","author":[{"given":"Jennifer L","family":"Chain","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison K","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas G","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"},{"name":"Department of Medicine, National Jewish Health , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent E","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P","family":"Fontenot","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"},{"name":"Department of Immunology, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"2025032405165795800_r1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.clim.2006.03.012","article-title":"T cell recognition in chronic beryllium disease","volume":"121","author":"Amicosante","year":"2006","journal-title":"Clin. 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