{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T08:26:31Z","timestamp":1759047991062},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2010,6,3]],"date-time":"2010-06-03T00:00:00Z","timestamp":1275523200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2010,6,3]],"date-time":"2010-06-03T00:00:00Z","timestamp":1275523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-\u03b1) that has been introduced recently for Beh\u00e7et's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of V\u03b39\/V\u03b42 T lymphocytes in both active and inactive disease and the effect of infliximab on V\u03b39\/V\u03b42 T cell expansion, activation and cytotoxicity.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, in V\u03b39\/V\u03b42 T lymphocytes by means of fluorescence-activated cell sorter analysis of lymphocyte cultures from patients with active and inactive BD and healthy subjects.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Cell expansion, expression of TNFRII, perforin and gamma IFN content and release of granzyme A were significantly higher in active patients. <jats:italic>In vitro<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> treatment with infliximab resulted in a significant reduction of all parameters together with changes in the phenotype of V\u03b39\/V\u03b42 T cells.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>All together these data indicate that infliximab is capable of interfering with V\u03b39\/V\u03b42 T cell function in BD and although cell culture models cannot reliably predict all potential effects of the drug <jats:italic>in vivo<\/jats:italic>, our results present the possibility that this drug may find use in a range of immunological disorders, characterized by dysregulated cell-mediated immunity.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3043","type":"journal-article","created":{"date-parts":[[2010,6,3]],"date-time":"2010-06-03T18:15:05Z","timestamp":1275588905000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Phenotype and functional changes of V\u03b39\/V\u03b42 T lymphocytes in Beh\u00e7et's disease and the effect of infliximab on V\u03b39\/V\u03b42 T cell expansion, activation and cytotoxicity"],"prefix":"10.1186","volume":"12","author":[{"given":"Antonina","family":"Accardo-Palumbo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Rita","family":"Giardina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Ciccia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Ferrante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Principato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalia","family":"Impastato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ennio","family":"Giardina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Triolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,6,3]]},"reference":[{"key":"2878_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/01.bor.0000197995.27579.9b","volume":"18","author":"N Pipitone","year":"2006","unstructured":"Pipitone N, Olivieri I, Cantini F, Triolo G, Salvarani C: New approaches in the treatment of Adamantiades-Beh\u00e7et's disease. Curr Opin Rheumatol. 2006, 18: 3-9. 10.1097\/01.bor.0000197995.27579.9b.","journal-title":"Curr Opin Rheumatol"},{"key":"2878_CR2","volume-title":"Rheumatol Int","author":"A Giardina","year":"2009","unstructured":"Giardina A, Ferrante A, Ciccia F, Vadal\u00e0 M, Giardina E, Triolo G: One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Beh\u00e7et's disease refractory to standard immunosuppressive drugs. Rheumatol Int. 2009."},{"key":"2878_CR3","first-page":"742","volume":"19","author":"A Kahan","year":"1992","unstructured":"Kahan A, Hamzaoui K, Ayed K: Abnormalities of T lymphocyte subsets in Beh\u00e7et' s disease demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies. J Rheumatol. 1992, 19: 742-746.","journal-title":"J Rheumatol"},{"key":"2878_CR4","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1136\/ard.61.5.459","volume":"61","author":"G Triolo","year":"2002","unstructured":"Triolo G, Accardo-Palumbo A, Dieli F, Ciccia F, Ferrante A, Giardina E, Licata G: Humoral and cell mediated immune response to cow's milk proteins in Beh\u00e7et's disease. Ann Rheum Dis. 2002, 61: 459-462. 10.1136\/ard.61.5.459.","journal-title":"Ann Rheum Dis"},{"key":"2878_CR5","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1002\/art.21145","volume":"52","author":"M Todaro","year":"2005","unstructured":"Todaro M, Zerilli M, Triolo G, Iovino F, Patti M, Accardo-Palumbo A, di Gaudio F, Turco MC, Petrella A, de Maria R, Stassi G: NF-kappaB protects Beh\u00e7et's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. Arthritis Rheum. 2005, 52: 2179-2191. 10.1002\/art.21145.","journal-title":"Arthritis Rheum"},{"key":"2878_CR6","doi-asserted-by":"publisher","first-page":"R262","DOI":"10.1186\/ar785","volume":"5","author":"G Triolo","year":"2003","unstructured":"Triolo G, Accardo-Palumbo A, Dieli F, Ciccia F, Ferrante A, Giardina E, Sano CD, Licata G: Vgamma9\/Vdelta2 T lymphocytes in Italian patients with Beh\u00e7et's disease: evidence for expansion, and humour necrosis factor receptor II and interleukin-12 receptor B1 expression in active disease. Arthritis Res Ther. 2003, 5: R262-R268. 10.1186\/ar785.","journal-title":"Arthritis Res Ther"},{"key":"2878_CR7","first-page":"S45","volume":"22","author":"A Accardo-Palumbo","year":"2004","unstructured":"Accardo-Palumbo A, Ferrante A, Cadelo M, Ciccia F, Parrinello G, Lipari L, Giardina AR, Riili M, Giardina E, Dieli F, Triolo G: The level of soluble Granzyme A is elevated in the plasma and in the Vgamma9\/Vdelta2 T cell culture supernatants of patients with active Beh\u00e7et's disease. Clin Exp Rheumatol. 2004, 22: S45-S49.","journal-title":"Clin Exp Rheumatol"},{"key":"2878_CR8","doi-asserted-by":"crossref","unstructured":"Criteria for diagnosis of Beh\u00e7et' s disease. International Study Group for Beh\u00e7et's Disease. Lancet. 1990, 335: 1078-1080.","DOI":"10.1016\/0140-6736(90)92643-V"},{"key":"2878_CR9","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/rheumatology\/38.8.728","volume":"38","author":"BB Bahcta","year":"1999","unstructured":"Bahcta BB, Brennan P, James TE, Chamberlain A, Noble BA, Silman AJ: Beh\u00e7et's disease: evaluation of a new instrument to measure clinical activity. Rheumatology. 1999, 38: 728-735. 10.1093\/rheumatology\/38.8.728.","journal-title":"Rheumatology"},{"key":"2878_CR10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/rheumatology\/keg453","volume":"43","author":"G Lawton","year":"2004","unstructured":"Lawton G, Bahcta BB, Chamberlain AA, Tennant A: The Beh\u00e7et's disease activity index. Rheumatology. 2004, 43: 73-78. 10.1093\/rheumatology\/keg453.","journal-title":"Rheumatology"},{"key":"2878_CR11","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.ajo.2005.03.057","volume":"140","author":"DA Jabs","year":"2005","unstructured":"Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group: Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophtalmol. 2005, 140: 509-516. 10.1016\/j.ajo.2005.01.035.","journal-title":"Am J Ophtalmol"},{"key":"2878_CR12","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/j.1365-2249.1990.tb05344.x","volume":"81","author":"K Hamzaoui","year":"1990","unstructured":"Hamzaoui K, Kahan A, Ayed K, Hamza M: Cytotoxic T cells against herpes simplex virus in Beh\u00e7et's disease. Clin Exp Immunol. 1990, 81: 390-395. 10.1111\/j.1365-2249.1990.tb05344.x.","journal-title":"Clin Exp Immunol"},{"key":"2878_CR13","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/0008-8749(92)90207-6","volume":"140","author":"S Hirohata","year":"1992","unstructured":"Hirohata S, Oka H, Mizushima Y: Streptococcal-related antigens stimulate production of IL-6 and interferon-gamma by T cells from patients with Beh\u00e7et's disease. Cell Immunol. 1992, 140: 410-419. 10.1016\/0008-8749(92)90207-6.","journal-title":"Cell Immunol"},{"key":"2878_CR14","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1002\/art.1780380321","volume":"38","author":"M Takeno","year":"1995","unstructured":"Takeno M, Kaiyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T: Excessive function of peripheral blood neutrophils from patients with Beh\u00e7et's disease and from HLA-B51 transgenic mice. Arthritis Rheum. 1995, 38: 426-433. 10.1002\/art.1780380321.","journal-title":"Arthritis Rheum"},{"key":"2878_CR15","first-page":"495","volume":"18","author":"A Accardo-Palumbo","year":"2000","unstructured":"Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Ciccia F, Giardina E, Triolo G: Polymorphonuclear leukocyte myeloperoxidase levels in patients with Beh\u00e7et's disease. Clin Exp Rheumatol. 2000, 18: 495-498.","journal-title":"Clin Exp Rheumatol"},{"key":"2878_CR16","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1006\/clim.1999.4687","volume":"91","author":"G Triolo","year":"1999","unstructured":"Triolo G, Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Giardina E: Enhancement of endothelial cell E-selectin expression by sera from patients with active Beh\u00e7et's disease: moderate correlation with anti-endothelial cell antibodies and myeloperoxidase levels. Clin Immunol. 1999, 91: 330-337. 10.1006\/clim.1999.4687.","journal-title":"Clin Immunol"},{"key":"2878_CR17","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1002\/art.1780251110","volume":"25","author":"T Sakane","year":"1982","unstructured":"Sakane T, Kotani H, Takada S, Tsunematsu T: Functional aberration of T cell subsets in patients with Beh\u00e7et's disease. Arthritis Rheum. 1982, 25: 1343-1351. 10.1002\/art.1780251110.","journal-title":"Arthritis Rheum"},{"key":"2878_CR18","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/j.1365-2249.1997.274-ce1159.x","volume":"107","author":"N Yamashita","year":"1997","unstructured":"Yamashita N, Kaneoka H, Nanako S, Oneda K, Koizumi H, Kogure M, Inaba G, Sakane T: Role of gammadelta T lymphocytes in the development of Beh\u00e7et's disease. Clin Exp Immunol. 1997, 107: 241-247. 10.1111\/j.1365-2249.1997.274-ce1159.x.","journal-title":"Clin Exp Immunol"},{"key":"2878_CR19","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1046\/j.1365-2249.1999.01069.x","volume":"118","author":"J Freysdottir","year":"1999","unstructured":"Freysdottir J, Lau S, Fortune F: \u03b3\u03b4 T cells in Beh\u00e7et's disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol. 1999, 118: 451-457. 10.1046\/j.1365-2249.1999.01069.x.","journal-title":"Clin Exp Immunol"},{"key":"2878_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/j.1365-3083.1995.tb03599.x","volume":"41","author":"F Spinozzi","year":"1995","unstructured":"Spinozzi F, Agea E, Bistoni O, Travetti A, Migliorati G, Moraca R, Nicoletti I, Riccardi C, Paoletti FP, Vaccaro R, et al: T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid-induced programmed cell death. Scand J Immunol. 1995, 41: 504-508. 10.1111\/j.1365-3083.1995.tb03599.x.","journal-title":"Scand J Immunol"},{"key":"2878_CR21","doi-asserted-by":"crossref","first-page":"4224","DOI":"10.4049\/jimmunol.155.9.4224","volume":"155","author":"T Lin","year":"1995","unstructured":"Lin T, Matsuzaki G, Umesue M, Omoto K, Yoshida H, Harada M, Singaram C, Hiromatsu K, Nomoto K: Development of TCR-gamma delta CD4-CD8+ alpha alpha but not TCR-alpha beta CD4-CD8+ alpha alpha i-IEL is resistant to cyclosporin A. J Immunol. 1995, 155: 4224-4230.","journal-title":"J Immunol"},{"key":"2878_CR22","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/039463200702000318","volume":"20","author":"A Accardo-Palumbo","year":"2007","unstructured":"Accardo-Palumbo A, Ferrante A, Ciccia F, Cadelo M, Giardina AR, Impastato R, Triolo G: Pentoxifylline inhibits Vgamma9\/Vdelta2 T lymphocyte activation of patients with active Beh\u00e7ets disease in vitro. Int J Immunopathol Pharmacol. 2007, 20: 601-606.","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2878_CR23","first-page":"1544","volume":"20","author":"JL Mege","year":"1993","unstructured":"Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H, Ocal L, Inanc M, Capo C: Overproduction of monocyte derived tumor necrosis factor \u03b1, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Beh\u00e7et' disease: a comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol. 1993, 20: 1544-1549.","journal-title":"J Rheumatol"},{"key":"2878_CR24","first-page":"321","volume":"23","author":"N Saynalp","year":"1996","unstructured":"Saynalp N, Ozcebe OL, Ozdemir O, Haznedaroglu IC, Dundar S, Kirazli S: Cytokines in Beh\u00e7et's disease. J Rheumatol. 1996, 23: 321-322.","journal-title":"J Rheumatol"},{"key":"2878_CR25","doi-asserted-by":"publisher","first-page":"3066","DOI":"10.1002\/eji.1830261237","volume":"26","author":"C Ueta","year":"1996","unstructured":"Ueta C, Kawasumi H, Fujiwarw H: Interleukin-12 activates human \u03b3\/\u03b4 T cells: synergistic effect of tumor necrosis factor-\u03b1. Eur J Immunol. 1996, 26: 3066-3073. 10.1002\/eji.1830261237.","journal-title":"Eur J Immunol"},{"key":"2878_CR26","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/0-306-48382-3_52","volume":"528","author":"AV Elezoglou","year":"2003","unstructured":"Elezoglou AV, Sfikakis PP, Vaiopoulos G, Kapsimali V, Kaklamanis PG: Serum levels of soluble TNF-alpha receptor-II (P75), circulating gammadelta T-cells and Adamantiades-Beh\u00e7et's disease activity. Adv Exp Med Biol. 2003, 528: 261-265. full_text.","journal-title":"Adv Exp Med Biol"},{"key":"2878_CR27","doi-asserted-by":"publisher","first-page":"7131","DOI":"10.4049\/jimmunol.181.10.7131","volume":"181","author":"H Li","year":"2008","unstructured":"Li H, Luo K, Pauza CD: TNF-alpha is a positive regulatory factor for human Vgamma2 Vdelta2 T cells. J Immunol. 2008, 181: 7131-7137.","journal-title":"J Immunol"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar3043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar3043\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar3043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T11:01:20Z","timestamp":1728385280000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar3043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,3]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,6]]}},"alternative-id":["2878"],"URL":"https:\/\/doi.org\/10.1186\/ar3043","relation":{},"ISSN":["1478-6354"],"issn-type":[{"type":"electronic","value":"1478-6354"}],"subject":[],"published":{"date-parts":[[2010,6,3]]},"assertion":[{"value":"26 February 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2010","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2010","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2010","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R109"}}