{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:31:31Z","timestamp":1770096691870,"version":"3.49.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T00:00:00Z","timestamp":1112313600000},"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":[[2005,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD4+ T cells play a key role in granulomatous inflammation in the lung of patients with chronic beryllium disease. The goal of this study was to characterize activation pathways of beryllium-responsive bronchoalveolar lavage (BAL) CD4+ T cells from chronic beryllium disease patients to identify possible therapeutic interventional strategies. Our results demonstrate that in the presence of APCs, beryllium induced strong proliferation responses of BAL CD4+ T cells, production of superoptimal concentrations of secreted proinflammatory cytokines, IFN-\u03b3, TNF-\u03b1,and IL-2, and up-regulation of numerous T cell surface markers that would promote T-T Ag presentation. Ab blocking experiments revealed that anti-HLA-DP or anti-LFA-1 Ab strongly reduced proliferation responses and cytokine secretion by BAL CD4+ T cells. In contrast, anti-HLA-DR or anti-OX40 ligand Ab mainly affected beryllium-induced proliferation responses with little impact on cytokines other than IL-2, thus implying that nonproliferating BAL CD4+ T cells may still contribute to inflammation. Blockade with CTLA4-Ig had a minimal effect on proliferation and cytokine responses, confirming that activation was independent of B7\/CD28 costimulation. These results indicate a prominent role for HLA-DP and LFA-1 in BAL CD4+ T cell activation and further suggest that specific Abs to these molecules could serve as a possible therapy for chronic beryllium disease.<\/jats:p>","DOI":"10.4049\/jimmunol.174.7.4316","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T22:39:15Z","timestamp":1398206355000},"page":"4316-4324","source":"Crossref","is-referenced-by-count":14,"title":["Activation Pathways Implicate Anti-HLA-DP and Anti-LFA-1 Antibodies as Lead Candidates for Intervention in Chronic Berylliosis"],"prefix":"10.1093","volume":"174","author":[{"given":"Yuan K","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Neuroimmunology Research, Veterans Affairs Medical Center , Portland, OR 97207"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center , Portland, OR 97213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A","family":"Vandenbark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Neuroimmunology Research, Veterans Affairs Medical Center , Portland, OR 97207"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L","family":"Kotzin","sequence":"additional","affiliation":[{"name":"Department of Medicine and Immunology, University of Colorado Health Sciences Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P","family":"Fontenot","sequence":"additional","affiliation":[{"name":"Department of Medicine and Immunology, University of Colorado Health Sciences Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory G","family":"Burrows","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Department of Biochemistry and Molecular Biology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,4,1]]},"reference":[{"key":"2026020212231492900_R1","first-page":"121","volume-title":"Crit. Rev. Clin. Lab. Sci.","year":"1995"},{"key":"2026020212231492900_R2","first-page":"221","volume-title":"Lancet","year":"2001"},{"key":"2026020212231492900_R3","first-page":"467","volume-title":"Rev. Mal. Respir.","year":"2002"},{"key":"2026020212231492900_R4","first-page":"1926","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020212231492900_R5","first-page":"398","volume-title":"J. Invest. Dermatol.","year":"1994"},{"key":"2026020212231492900_R6","first-page":"161","volume-title":"Toxicology","year":"1997"},{"key":"2026020212231492900_R7","first-page":"108","volume-title":"Allergy","year":"2000"},{"key":"2026020212231492900_R8","first-page":"367","volume-title":"Interstitial Lung Disease","year":"1998"},{"key":"2026020212231492900_R9","first-page":"415","volume-title":"Lancet","year":"2004"},{"key":"2026020212231492900_R10","first-page":"1103","volume-title":"N. Engl. J. Med.","year":"1989"},{"key":"2026020212231492900_R11","first-page":"12717","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026020212231492900_R12","first-page":"242","volume-title":"Science","year":"1993"},{"key":"2026020212231492900_R13","first-page":"6910","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212231492900_R14","first-page":"1884","volume-title":"Am. J. Respir. Crit. Care Med.","year":"1997"},{"key":"2026020212231492900_R15","first-page":"518","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020212231492900_R16","first-page":"687","volume-title":"Ann. Intern. Med.","year":"1988"},{"key":"2026020212231492900_R17","first-page":"1473","volume-title":"J. Clin. Invest.","year":"2002"},{"key":"2026020212231492900_R18","first-page":"3627","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020212231492900_R19","first-page":"1123","volume-title":"J. Exp. Med.","year":"1990"},{"key":"2026020212231492900_R20","first-page":"138","volume-title":"Lab. Invest.","year":"1992"},{"key":"2026020212231492900_R21","first-page":"581","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"1998"},{"key":"2026020212231492900_R22","first-page":"607","volume-title":"Nature","year":"1992"},{"key":"2026020212231492900_R23","first-page":"555","volume-title":"Immunity","year":"1995"},{"key":"2026020212231492900_R24","first-page":"935","volume-title":"Immunity","year":"2001"},{"key":"2026020212231492900_R25","first-page":"776","volume-title":"J. Clin. Invest.","year":"2003"},{"key":"2026020212231492900_R26","first-page":"420","volume-title":"Nat. Rev.","year":"2004"},{"key":"2026020212231492900_R27","first-page":"286","volume-title":"Curr. Opin. Immunol.","year":"1999"},{"key":"2026020212231492900_R28","first-page":"3043","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020212231492900_R29","first-page":"1019","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020212231492900_R30","first-page":"953","volume-title":"Environ. Health Perspect.","year":"1996"},{"key":"2026020212231492900_R31","first-page":"1479","volume-title":"Am. Rev. Respir. Dis.","year":"1989"},{"key":"2026020212231492900_R32","first-page":"1724","volume-title":"J. Natl. Cancer Inst.","year":"2001"},{"key":"2026020212231492900_R33","first-page":"838","volume-title":"J. Neurosci. Res.","year":"1996"},{"key":"2026020212231492900_R34","first-page":"1172","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212231492900_R35","first-page":"98","volume-title":"Cell Immunol.","year":"2002"},{"key":"2026020212231492900_R36","first-page":"293","volume-title":"J. Immunol.","year":"1980"},{"key":"2026020212231492900_R37","first-page":"179","volume-title":"Immunogenetics","year":"1984"},{"key":"2026020212231492900_R38","first-page":"301","volume-title":"Hum. Immunol.","year":"1987"},{"key":"2026020212231492900_R39","first-page":"2675","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020212231492900_R40","first-page":"962","volume-title":"J. Leukocyte Biol.","year":"2004"},{"key":"2026020212231492900_R41","first-page":"9","volume-title":"Toxicology","year":"2004"},{"key":"2026020212231492900_R42","first-page":"155","volume-title":"Toxicology","year":"1999"},{"key":"2026020212231492900_R43","first-page":"135","volume-title":"Am. J. Respir. Crit. Care Med.","year":"1994"},{"key":"2026020212231492900_R44","first-page":"708","volume-title":"Nature","year":"1999"},{"key":"2026020212231492900_R45","first-page":"1909","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2026020212231492900_R46","first-page":"521","volume-title":"Clin. Cancer Res.","year":"2004"},{"key":"2026020212231492900_R47","first-page":"721","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020212231492900_R48","first-page":"10638","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026020212231492900_R49","first-page":"813","volume-title":"Cell","year":"1987"},{"key":"2026020212231492900_R50","first-page":"2530","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020212231492900_R51","first-page":"1270","volume-title":"J. Immunol.","year":"1986"},{"key":"2026020212231492900_R52","first-page":"185","volume-title":"J. Exp. Med.","year":"1992"},{"key":"2026020212231492900_R53","first-page":"159","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026020212231492900_R54","first-page":"2285","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020212231492900_R55","first-page":"2528","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020212231492900_R56","first-page":"6009","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026020212231492900_R57","first-page":"6510","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020212231492900_R58","first-page":"107","volume-title":"J. Immunol.","year":"2000"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/174\/7\/4316\/62613151\/4316.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/174\/7\/4316\/62613151\/4316.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T17:29:39Z","timestamp":1770053379000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/174\/7\/4316\/8036627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,1]]},"references-count":58,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2005,4,1]]},"published-print":{"date-parts":[[2005,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.174.7.4316","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,4]]},"published":{"date-parts":[[2005,4,1]]}}}