{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T01:13:04Z","timestamp":1770426784069,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T00:00:00Z","timestamp":1080259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies in experimental animal models of human autoimmune diseases have revealed that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto\u2010aggressive immunity. Myasthenia gravis (MG) is the best\u2010characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> versus CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2013<\/jats:sup> cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup> cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup> cells were similar in MG patients irrespective of treatment with thymectomy. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2013<\/jats:sup> cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)\u2010DR\u2010positive cells. In both MG patients and HCs, CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells also contained a high proportion of CD95\u2010expressing cells as possible evidence of apoptosis\u2010proneness. Upon stimulation with anti\u2010CD3\/CD28 monoclonal antibodies, CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells responded more vigorously than CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2013<\/jats:sup> cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2013<\/jats:sup> cells are mainly na\u00efve T cells, in non\u2010thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA\u2010DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells in MG, nor is the proportion of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells influenced by thymectomy.<\/jats:p>","DOI":"10.1111\/j.0300-9475.2004.01410.x","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T16:14:53Z","timestamp":1080317693000},"page":"408-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Circulating CD4<sup>+<\/sup>CD25<sup>+<\/sup> and CD4<sup>+<\/sup>CD25<sup>\u2013<\/sup> T Cells in Myasthenia Gravis and in Relation to Thymectomy"],"prefix":"10.1111","volume":"59","author":[{"given":"Y.\u2010M.","family":"Huang","sequence":"first","affiliation":[]},{"given":"R.","family":"Pirskanen","sequence":"additional","affiliation":[]},{"given":"R.","family":"Giscombe","sequence":"additional","affiliation":[]},{"given":"H.","family":"Link","sequence":"additional","affiliation":[]},{"given":"A.\u2010K.","family":"Lefvert","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2004,3,26]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"455","article-title":"Cells: key controllers of immunological self\u2010tolerance","volume":"2000","author":"Sakaguchi S","journal-title":"Cell"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm924"},{"key":"e_1_2_6_4_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 a\u2010chains (CD25). Breakdown of a single mechanism of self\u2010tolerance causes various autoimmune diseases","volume":"160","author":"Sakaguchi S","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.6.2393"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.4049\/jimmunol.160.3.1212","article-title":"CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells","volume":"160","author":"Suri\u2010Payer E","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.4049\/jimmunol.162.9.5317","article-title":"Thymus and autoimmunity. production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self\u2010tolerance","volume":"162","author":"Itoh M","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf105"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.9.1213"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.11.1303"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200104)31:4<1247::AID-IMMU1247>3.0.CO;2-M"},{"key":"e_1_2_6_12_2","first-page":"1129","article-title":"CD4+CD25+ T\u2010cell population in healthy humans and in patients with thymic hypoplasia","volume":"9","author":"Sullivan KE","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/immu.200390024"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri916"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406233302507"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.1.7"},{"key":"e_1_2_6_17_2","first-page":"55","article-title":"A histological reappraisal of the thymus in myasthenia gravis. A correlative study of thymic pathology and response to thymectomy","volume":"91","author":"Alpert LI","year":"1971","journal-title":"Arch Pathol"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01412.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.11.1311"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni939"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(64)90171-6"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.1820102.x"},{"key":"e_1_2_6_23_2","first-page":"8643","article-title":"Depletion of CD4+CD25+ T cells and treatment wit tyrosinase\u2010related protein 2\u2010transduced dendritic cells enhance the interferon alpha\u2010induced CD8(+) T cell\u2010dependent immune defense of B16 melanoma","volume":"61","author":"Steitz J","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.9.4272"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020090"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020399"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-6143.2003.00124.x"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)49895-X"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1245"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200104)31:4<1122::AID-IMMU1122>3.0.CO;2-P"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(96)00204-4"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.5979"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar624"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2003.08.001"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2003.09.011"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2003.00293.x"}],"container-title":["Scandinavian Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.0300-9475.2004.01410.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.0300-9475.2004.01410.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T04:35:09Z","timestamp":1696912509000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.0300-9475.2004.01410.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,26]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1111\/j.0300-9475.2004.01410.x"],"URL":"https:\/\/doi.org\/10.1111\/j.0300-9475.2004.01410.x","archive":["Portico"],"relation":{},"ISSN":["0300-9475","1365-3083"],"issn-type":[{"value":"0300-9475","type":"print"},{"value":"1365-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3,26]]},"assertion":[{"value":"2004-03-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}