{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:53:11Z","timestamp":1790855591243,"version":"4.1.0"},"reference-count":111,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Although human and experimental acquired myasthenia gravis (MG) are prototypic antibody (Ab)\u2010mediated autoimmune diseases, synthesis of the pathogenic anti\u2010acetylcholine receptor (AChR) Abs, which are high affinity IgG, requires intervention of CD4<jats:sup>+<\/jats:sup> T helper cells and their cytokines. Moreover, cytokine signaling is crucial for development, modulation, and downregulation of immune responses, and therefore influences the initiation and evolution of the anti\u2010AChR response in acquired MG. Cytokines are involved in the growth and differentiation of CD4<jats:sup>+<\/jats:sup> T cells, and are secreted by activated CD4<jats:sup>+<\/jats:sup> T cells as effectors of their functions: differentiated CD4<jats:sup>+<\/jats:sup> T cells are classified into subtypes based on the cytokines they synthesize and secrete. Because cytokines are synthesized by and act on a variety of cells and because they may influence the synthesis and\/or the activity of other cytokines, the effects of their signaling, in both normal and autoimmune responses, are complex and sometimes even contrasting, depending on the circumstances when the cytokine action took place. In this chapter, we will review studies on the effects on the development of acquired MG symptoms of several cytokines secreted by activated CD4<jats:sup>+<\/jats:sup> T cells or influencing the activation of particular CD4<jats:sup>+<\/jats:sup> T cell subsets.<\/jats:p>","DOI":"10.1196\/annals.1405.042","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T23:23:28Z","timestamp":1214004208000},"page":"193-209","source":"Crossref","is-referenced-by-count":51,"title":["<i>CD4<sup>+<\/sup> T Cells and Cytokines in the Pathogenesis of Acquired Myasthenia Gravis<\/i>"],"prefix":"10.1111","volume":"1132","author":[{"given":"Bianca M.","family":"Conti\u2010Fine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Milani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_10_2_2","volume-title":"Myasthenia Gravis: The Immunobiology of an Autoimmune Disease","author":"Conti\u2010Fine B.M.","year":"1997"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29894"},{"key":"e_1_2_10_4_2","first-page":"159","article-title":"Myasthenia gravis","volume":"88","author":"Vincent A.","year":"2002","journal-title":"Adv. Neurol."},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.151.1.204"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.141.6.1365"},{"key":"e_1_2_10_7_2","first-page":"267","article-title":"Immune complexes (IgG and C3) at the motor end\u2010plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations","volume":"52","author":"Engel A.G.","year":"1977","journal-title":"Mayo Clin. Proc."},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198003000-00005"},{"key":"e_1_2_10_9_2","first-page":"78","article-title":"Myasthenia gravis: demonstration of membrane attack complex in muscle end\u2010plates","volume":"5","author":"Fazekas A.","year":"1986","journal-title":"Clin. Neuropathol."},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.147.4.973"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.142.8.2654"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(96)00144-0"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.8.2589"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5236"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.3.848"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114196"},{"key":"e_1_2_10_17_2","first-page":"532","article-title":"Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues","volume":"65","author":"Meri S.","year":"1991","journal-title":"Lab. Invest."},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01287.x"},{"key":"e_1_2_10_19_2","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.4049\/jimmunol.155.6.3079","article-title":"Molecular cloning and chromosomal localization of the mouse decay\u2010accelerating factor genes. Duplicated genes encode glycosylphosphatidylinositol\u2010anchored and transmembrane forms","volume":"155","author":"Spicer A.P.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216086"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830171232"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/310244a0"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.5.734"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.9.1732"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.40.4.581"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.3.484"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.6.3152"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117050"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.1045"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00250-2"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.19.7792"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.018"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.566"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/383787a0"},{"key":"e_1_2_10_35_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/00054725-199911000-00009","article-title":"Th1\/Th2 cells","volume":"5","author":"Romagnani S.","year":"1999","journal-title":"Inflammatory Bowel Dis."},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.001"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.1820117.x"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)01573-3"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)90044-2"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.4853"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00385-4"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.2.1077"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2487::AID-IMMU2487>3.0.CO;2-Y"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00474-X"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.10.1381"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(00)00005-8"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80505-1"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00199-X"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.170138"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.152.3.507"},{"key":"e_1_2_10_51_2","first-page":"247","article-title":"Immunogenetics of experimental autoimmune myasthenia gravis","volume":"9","author":"Christadoss P.","year":"1989","journal-title":"Crit. Rev. Immunol."},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830211003"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.1.97"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)91330-9"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI14255"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90095-3"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.3.385"},{"key":"e_1_2_10_58_2","first-page":"503","article-title":"Induction of HLA\u2010DR expression on human myoblasts with interferon\u2010gamma","volume":"136","author":"Hohlfeld R.","year":"1990","journal-title":"Am. J. Pathol."},{"key":"e_1_2_10_59_2","first-page":"1","article-title":"Interferon\u2010gamma, interleukin\u20104 and transforming growth factor\u2010beta mRNA expression in multiple sclerosis and myasthenia gravis","volume":"158","author":"Link J.","year":"1994","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2000.4850"},{"key":"e_1_2_10_61_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5324"},{"key":"e_1_2_10_62_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5050"},{"key":"e_1_2_10_63_2","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.4049\/jimmunol.162.7.3775","article-title":"Mice with IFN\u2010gamma receptor deficiency are less susceptible to experimental autoimmune myasthenia gravis","volume":"162","author":"Zhang G.X.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_10_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(93)90195-5"},{"key":"e_1_2_10_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.11.6368"},{"key":"e_1_2_10_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92863-7"},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.1.5"},{"key":"e_1_2_10_68_2","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.4049\/jimmunol.157.8.3223","article-title":"IFN\u2010gamma plays a critical down\u2010regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein\u2010induced autoimmune encephalomyelitis","volume":"157","author":"Willenborg D.O.","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_10_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.6.3143"},{"key":"e_1_2_10_70_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.8.1225"},{"key":"e_1_2_10_71_2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.4049\/jimmunol.162.1.510","article-title":"IFN\u2010gamma increases the severity and accelerates the onset of experimental autoimmune uveitis in transgenic rats","volume":"162","author":"Egwuagu C.E.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_10_72_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.12.5997"},{"key":"e_1_2_10_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/346844a0"},{"key":"e_1_2_10_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-8411(91)90021-4"},{"key":"e_1_2_10_75_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115055"},{"key":"e_1_2_10_76_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.6.812"},{"key":"e_1_2_10_77_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6173"},{"key":"e_1_2_10_78_2","doi-asserted-by":"crossref","first-page":"890","DOI":"10.4049\/jimmunol.152.2.890","article-title":"Endogenous systemic IFN\u2010gamma has a protective role against ocular autoimmunity in mice","volume":"152","author":"Caspi R.R.","year":"1994","journal-title":"J. Immunol."},{"key":"e_1_2_10_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.06.001"},{"key":"e_1_2_10_80_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.7072"},{"key":"e_1_2_10_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207577200"},{"key":"e_1_2_10_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.04.005"},{"key":"e_1_2_10_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700004"},{"key":"e_1_2_10_84_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.3.1151"},{"key":"e_1_2_10_85_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020509"},{"key":"e_1_2_10_86_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1500"},{"key":"e_1_2_10_87_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050419"},{"key":"e_1_2_10_88_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3900"},{"key":"e_1_2_10_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.04.005"},{"key":"e_1_2_10_90_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200423594"},{"key":"e_1_2_10_91_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01147.x"},{"key":"e_1_2_10_92_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7898"},{"key":"e_1_2_10_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/79792"},{"key":"e_1_2_10_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00262-8"},{"key":"e_1_2_10_95_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.1.604"},{"key":"e_1_2_10_96_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb10983.x"},{"key":"e_1_2_10_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00030-9"},{"key":"e_1_2_10_98_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.297"},{"key":"e_1_2_10_99_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117354"},{"key":"e_1_2_10_100_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.757"},{"key":"e_1_2_10_101_2","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.4049\/jimmunol.154.6.2533","article-title":"Endogenous IL\u20106 and IL\u201010 contribute to the differentiation of CD40\u2010activated human B lymphocytes","volume":"154","author":"Burdin N.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_10_102_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.8.1243"},{"key":"e_1_2_10_103_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.937"},{"key":"e_1_2_10_104_2","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.4049\/jimmunol.160.5.2145","article-title":"CD40 ligand and appropriate cytokines induce switching to IgG, IgA, and IgE and coordinated germinal center and plasmacytoid phenotypic differentiation in a human monoclonal IgM+IgD+ B cell line","volume":"160","author":"Cerutti A.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_10_105_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.12.2101"},{"key":"e_1_2_10_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80533-6"},{"key":"e_1_2_10_107_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4432"},{"key":"e_1_2_10_108_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.01062.x"},{"key":"e_1_2_10_109_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.3.839"},{"key":"e_1_2_10_110_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050456"},{"key":"e_1_2_10_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80070-0"},{"key":"e_1_2_10_112_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.6.603"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1405.042","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1405.042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T02:25:17Z","timestamp":1695695117000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1405.042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6]]},"references-count":111,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1196\/annals.1405.042"],"URL":"https:\/\/doi.org\/10.1196\/annals.1405.042","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6]]}}}