{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:14:43Z","timestamp":1774563283604,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1998,4,1]],"date-time":"1998-04-01T00:00:00Z","timestamp":891388800000},"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":[[1998,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic beryllium disease (CBD) is a granulomatous disorder characterized by the presence of noncaseating granulomas and mononuclear cell inflammation, occurring in 1 to 5% of people exposed to beryllium in the workplace. In the lungs of affected patients, CD4+ T cells accumulate. Using anti-T-cell receptor (TCR) monoclonal antibodies, we investigated the TCR beta and alpha variable (V\u03b2 and V\u03b1, respectively) repertoire in the bronchoalveolar lavage (BAL) and blood of both CBD patients and healthy controls. There was marked heterogeneity within the BAL CD4+ T-cell repertoire in both patients and controls. However, 11 of the 28 CBD patients demonstrated 16 different T-cell subset expansions within the BAL as compared with only one expansion in ten healthy controls. Five of the 16 expansions in CBD patients expressed V\u03b23. Altered TCR expression within the BAL T-cell repertoire appeared to persist over time in patients who underwent repeat evaluation. After in vitro stimulation of BAL T cells with beryllium sulfate and interleukin-2, we noted further alteration of the BAL TCR repertoire in some individuals. These results provide additional insight into the involvement of CD4+ T cells in this disease and form the basis for studies to examine the nature of the stimulating antigen.<\/jats:p>","DOI":"10.1165\/ajrcmb.18.4.2981","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:11:11Z","timestamp":1365027071000},"page":"581-589","source":"Crossref","is-referenced-by-count":60,"title":["Expansions of T-cell Subsets Expressing Particular T-cell Receptor Variable Regions in Chronic Beryllium Disease"],"prefix":"10.1093","volume":"18","author":[{"given":"Andrew P.","family":"Fontenot","sequence":"first","affiliation":[{"name":"Departments of Medicine and Pediatrics, National Jewish Medical and Research Center; and Departments of Medicine, Preventive Medicine and Biometrics, and Immunology, University of Colorado Health Sciences Center, Denver, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L.","family":"Kotzin","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, National Jewish Medical and Research Center; and Departments of Medicine, Preventive Medicine and Biometrics, and Immunology, University of Colorado Health Sciences Center, Denver, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"Comment","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, National Jewish Medical and Research Center; and Departments of Medicine, Preventive Medicine and Biometrics, and Immunology, University of Colorado Health Sciences Center, Denver, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee S.","family":"Newman","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, National Jewish Medical and Research Center; and Departments of Medicine, Preventive Medicine and Biometrics, and Immunology, University of Colorado Health Sciences Center, Denver, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1998,4,1]]},"reference":[{"key":"2026030700192266100_B1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1056\/NEJM198904273201702","article-title":"Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells.","volume":"320","author":"Saltini","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"2026030700192266100_B2","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1378\/chest.109.3_Supplement.40S","article-title":"Immunology, genetics, and epidemiology of beryllium disease.","volume":"109(Suppl.)","author":"Newman","year":"1996","journal-title":"Chest"},{"key":"2026030700192266100_B3"},{"key":"2026030700192266100_B4","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1164\/ajrccm\/137.2.464","article-title":"The pulmonary toxicity of beryllium.","volume":"137","author":"Kriebel","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700192266100_B5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0046-8177(70)80003-X","article-title":"Beryllium disease: the relation of pulmonary pathology to the clinical course and prognosis based on a study of 130 cases from the U.S. Beryllium Case Registry.","volume":"1","author":"Freiman","year":"1970","journal-title":"Hum. Pathol."},{"key":"2026030700192266100_B6","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1164\/ajrccm\/139.6.1479","article-title":"Pathologic and immunologic alterations in early stages of beryllium disease: re-examination of disease definition and natural history.","volume":"139","author":"Newman","year":"1989","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700192266100_B7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1164\/ajrccm.150.1.8025739","article-title":"Compartmentalized immune response reflects clinical severity of beryllium disease.","volume":"150","author":"Newman","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026030700192266100_B8","doi-asserted-by":"crossref","first-page":"687","DOI":"10.7326\/0003-4819-108-5-687","article-title":"Proliferative response of bronchoalveolar lymphocytes to beryllium.","volume":"108","author":"Rossman","year":"1988","journal-title":"Ann. Intern. Med."},{"key":"2026030700192266100_B9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.7326\/0003-4819-97-2-213","article-title":"Bronchoalveolar lavage in a patient with chronic berylliosis: evidence for hypersensitivity pneumonitis.","volume":"97","author":"Epstein","year":"1982","journal-title":"Ann. Intern. Med."},{"key":"2026030700192266100_B10","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4049\/jimmunol.158.1.518","article-title":"Beryllium induces IL-2 and IFN-\u03b3 in berylliosis.","volume":"158","author":"Tinkle","year":"1997","journal-title":"J. Immunol."},{"key":"2026030700192266100_B11","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1164\/ajrccm\/145.5.1212","article-title":"Nonoccupational beryllium disease masquerading as sarcoidosis: identification by blood lymphocyte proliferation response to beryllium.","volume":"145","author":"Newman","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700192266100_B12","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.1073\/pnas.91.11.4965","article-title":"T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.","volume":"91","author":"Grunewald","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700192266100_B13","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1172\/JCI113715","article-title":"Bias toward use of a specific T cell receptor \u03b2-chain variable region in a subgroup of individuals with sarcoidosis.","volume":"82","author":"Moller","year":"1988","journal-title":"J. Clin. Invest."},{"key":"2026030700192266100_B14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/eji.1830220120","article-title":"Restricted V\u03b12.3 gene usage by CD4+ T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients correlates with HLA-DR3.","volume":"22","author":"Grunewald","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2026030700192266100_B15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0091-6749(91)90300-D","article-title":"Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease.","volume":"88","author":"Mroz","year":"1991","journal-title":"J. Allergy Clin. Immunol"},{"key":"2026030700192266100_B16","first-page":"S168","article-title":"Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis and selected comparison groups.","volume":"141(Suppl.)","author":"The BAL Cooperative Group Steering Committee","year":"1990","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700192266100_B17","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1002\/eji.1830221043","article-title":"A versatile method to produce antibodies to human T cell receptor V beta segments: frequency determinations of human V beta 2+ T cells that react with toxic-shock syndrome toxin-1.","volume":"22","author":"Romagne","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2026030700192266100_B18","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.179.5.1701","article-title":"Genetic analysis of low V beta 3 expression in humans.","volume":"179","author":"Donahue","year":"1994","journal-title":"J. Exp. Med."},{"key":"2026030700192266100_B19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0022-1759(93)90316-Y","article-title":"Characterization of monoclonal antibodies specific for the V\u03b23 family of the T cell receptor generated using soluble TCR \u03b2-chain.","volume":"164","author":"Calaman","year":"1993","journal-title":"J. Immunol. Methods"},{"key":"2026030700192266100_B20","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/eji.1830161002","article-title":"T cell clones which share T cell receptor epitopes differ in phenotype, function, and specificity.","volume":"16","author":"Yssel","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"2026030700192266100_B21","doi-asserted-by":"crossref","first-page":"7888","DOI":"10.1073\/pnas.83.20.7888","article-title":"Inherited polymorphism of the human T-cell antigen receptor detected by a monoclonal antibody.","volume":"83","author":"Posnett","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700192266100_B22","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/eji.1830160610","article-title":"Expression on human thymocytes of the idiopathic structures (Ti) from two leukemia T cell lines Jurkat and HPB-ALL.","volume":"16","author":"Carrel","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"2026030700192266100_B23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1126\/science.2524876","article-title":"V\u03b2-specific stimulation of human T cells by staphylococcal toxins.","volume":"244","author":"Kappler","year":"1989","journal-title":"Science"},{"key":"2026030700192266100_B24","doi-asserted-by":"crossref","first-page":"8357","DOI":"10.1073\/pnas.88.19.8357","article-title":"A method for production of antibodies to human T-cell receptor \u03b2-chain variable regions.","volume":"88","author":"Choi","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700192266100_B25"},{"key":"2026030700192266100_B26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1172\/JCI116184","article-title":"Clonal expansion of lung V\u03b41+ T cells in pulmonary sarcoidosis.","volume":"91","author":"Forrester","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2026030700192266100_B27","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1165\/ajrcmb.10.5.8179912","article-title":"Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-\u03b1 and interleukin-6 but not interleukin-1\u03b2.","volume":"10","author":"Bost","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700192266100_B28","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.4049\/jimmunol.153.9.4291","article-title":"TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis.","volume":"153","author":"Forrester","year":"1994","journal-title":"J. Immunol."},{"key":"2026030700192266100_B29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1055\/s-2007-1012616","article-title":"Chronic beryllium disease in the United States.","volume":"7","author":"Cullen","year":"1986","journal-title":"Sem. Respir. Med."},{"key":"2026030700192266100_B30","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1097\/00043764-198907000-00011","article-title":"Screening blood test identifies subclinical beryllium disease.","volume":"31","author":"Kreiss","year":"1989","journal-title":"J. Occup. Med."},{"key":"2026030700192266100_B31","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.4049\/jimmunol.150.9.4085","article-title":"Diverse T cell receptor V\u03b2 gene usage in the central nervous system in experimental allergic encephalomyelitis.","volume":"150","author":"Bell","year":"1993","journal-title":"J. Immunol."},{"key":"2026030700192266100_B32","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.4049\/jimmunol.154.7.3538","article-title":"Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis.","volume":"154","author":"Fitzgerald","year":"1995","journal-title":"J. Immunol."},{"key":"2026030700192266100_B33","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1172\/JCI117494","article-title":"Selective activation and accumulation of oligoclonal V\u03b2-specific T cells in active pulmonary sarcoidosis.","volume":"94","author":"Forman","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2026030700192266100_B34","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.8105536","article-title":"HLA-DPB1 glutamate 69: a genetic marker of beryllium disease.","volume":"262","author":"Richeldi","year":"1993","journal-title":"Science"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/18\/4\/581\/67212714\/ajrcmb_18_4_581.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/18\/4\/581\/67212714\/ajrcmb_18_4_581.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T05:28:33Z","timestamp":1772861313000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/18\/4\/581\/8504493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,4,1]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1998,4,1]]},"published-print":{"date-parts":[[1998,4,1]]}},"URL":"https:\/\/doi.org\/10.1165\/ajrcmb.18.4.2981","relation":{},"ISSN":["1535-4989","1044-1549"],"issn-type":[{"value":"1535-4989","type":"electronic"},{"value":"1044-1549","type":"print"}],"subject":[],"published-other":{"date-parts":[[1998,4]]},"published":{"date-parts":[[1998,4,1]]}}}