{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:00:18Z","timestamp":1774926018995,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,7,4]],"date-time":"2008-07-04T00:00:00Z","timestamp":1215129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Recently, forkhead box P3 (Foxp3), cytotoxic T\u2010lymphocyte\u2010associated antigen\u20104 (CTLA\u20104), glucocorticoid\u2010induced tumor necrosis factor receptor family\u2010related gene (GITR), and CD28 were identified as the key molecules that control the development and activation of CD4+CD25+ regulatory T cells (T\u2010reg). We investigated the expression pattern of these molecules on T\u2010reg, and investigated the ability of T\u2010reg to produce cytokines in patients with autoimmune hepatitis (AIH).<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Fifteen patients with AIH and nine healthy patients were included. To determine the frequency of T\u2010reg, a two\u2010color flow cytometry analysis was performed. T\u2010reg were isolated using immunomagnetic beads, and the mRNA levels of <jats:italic>Foxp3<\/jats:italic>, <jats:italic>CTLA\u20104, GITR<\/jats:italic>, and <jats:italic>CD28<\/jats:italic> were quantified by real\u2010time polymerase chain reaction (PCR). The ability of T\u2010reg to produce interferon\u2010\u03b3, interleukin (IL)\u201010, transforming growth factor\u2010\u03b2, and tumor necrosis factor\u2010\u03b1 after stimulation by OKT3 was evaluated by measuring the levels of mRNA in T\u2010reg by real\u2010time PCR.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The frequency of T\u2010reg was increased in AIH. The mRNA levels of <jats:italic>Foxp3<\/jats:italic> and <jats:italic>CTLA\u20104<\/jats:italic> were significantly lower in AIH. The ability of T\u2010reg to produce IL\u201010 was impaired in AIH.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> We speculate that the inferiority of the Foxp3 and CTLA\u20104 gene expressions on T\u2010reg results in the impaired suppressor function of T\u2010reg, and eventually in the breakdown of self\u2010tolerance.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2008.00349.x","type":"journal-article","created":{"date-parts":[[2008,7,6]],"date-time":"2008-07-06T00:16:59Z","timestamp":1215303419000},"page":"896-903","source":"Crossref","is-referenced-by-count":29,"title":["Deficiency of forkhead box P3 and cytotoxic T\u2010lymphocyte\u2010associated antigen\u20104 gene expressions and impaired suppressor function of CD4<sup>+<\/sup>CD25<sup>+<\/sup> T cells in patients with autoimmune hepatitis"],"prefix":"10.1111","volume":"38","author":[{"given":"Akihiko","family":"Okumura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taeko","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisae","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Ayada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Hotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Kakumu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,8,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.1820104.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1245"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00415.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.12.1969"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3008"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.2.834"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.387"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self\u2010tolerance maintained by activated T cells expressing IL\u20102 receptor alpha\u2010chains (CD25). Breakdown of a single mechanism of self\u2010tolerance causes various autoimmune diseases","volume":"115","author":"Sakaguchi S","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020090"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01152"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151174198"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni909"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni759"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.1820102.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007318"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21518"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.12.019"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(02)00023-5"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113949"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1992.tb02983.x"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1016\/0016-5085(93)90657-X","article-title":"Characterization of anti\u2010liver\u2010kidney microsome antibody (anti\u2010LKM1) from hepatitis C virus\u2010positive and \u2013 negative sera","volume":"104","author":"Yamamoto AM","year":"1993","journal-title":"Gastroenterology"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.4.449"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.3.1481"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21658"},{"key":"e_1_2_6_27_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hep.1840200104","article-title":"Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIA Cooperative Study Group","volume":"20","author":"METAVIA.","year":"1994","journal-title":"Hepatology"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hep.2003.09.022"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840180435"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-005-1713-x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.225"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.303"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.295"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4376"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80195-8"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.03.008"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030315"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030422"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030654"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.183"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4484"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1872-034X.2008.00349.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1872-034X.2008.00349.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T17:07:01Z","timestamp":1697389621000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1872-034X.2008.00349.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,5]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1111\/j.1872-034X.2008.00349.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1872-034x.2008.00349.x","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,5]]}}}