{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:55:11Z","timestamp":1761216911583},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,4,15]],"date-time":"2005-04-15T00:00:00Z","timestamp":1113523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CD8<jats:sup>+<\/jats:sup> T\u2004cells play an important role in the induction of the autoimmune response in non\u2010obese diabetic (NOD) mice. Here we describe abnormalities in the control of cytokine production by NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells. NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells had an increased propensity to produce IFN\u2010\u03b3 upon TCR activation, in both adult and 2\u2010week\u2010old mice. NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells had a reduced capacity to produce IL\u20104 in type\u20042 conditions compared to CD8<jats:sup>+<\/jats:sup> T\u2004cells from the diabetes\u2010resistant strains BALB\/c and C57BL\/6. Both GATA\u20103 and c\u2010Maf, two positive transactivators for IL\u20104 gene expression, were expressed in type\u20042 conditions at comparable levels in NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells. The GATA\u20103 was functional since normal levels of IL\u20105 were produced and the IL\u20104 promoter was hyperacetylated in NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells. In contrast, c\u2010Maf failed to bind to its responsive element as determined by chromatin immunoprecipitation (ChIP) assay. These results suggest that NOD CD8<jats:sup>+<\/jats:sup> T\u2004cells possess an increased propensity to produce IFN\u2010\u03b3 and impaired c\u2010Maf\u2010dependent DNA binding activities <jats:italic>in vivo<\/jats:italic> that lead to reduced IL\u20104 production following TCR activation. These defects may facilitate the development of the autoimmune response by inducing an overall type\u20041\u2010biased immune response in NOD mice.<\/jats:p>","DOI":"10.1002\/eji.200425483","type":"journal-article","created":{"date-parts":[[2005,4,15]],"date-time":"2005-04-15T10:17:32Z","timestamp":1113560252000},"page":"1408-1417","source":"Crossref","is-referenced-by-count":8,"title":["Impaired IL\u20104 production by CD8<sup>+<\/sup> T\u2004cells in NOD mice is related to a defect of c\u2010Maf binding to the IL\u20104 promoter"],"prefix":"10.1002","volume":"35","author":[{"given":"Xiao\u2010Ping","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dewayne\u2004H.","family":"Falkner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope\u2004A.","family":"Morel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,4,22]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1999.0322"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2966437"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260815"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/10446670310001626508"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191383798"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2003.00013.x"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1288.010"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6266"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80178-6"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.4.613"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6580"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.2.735"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.1.188"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.2002.0597"},{"key":"e_1_2_7_15_2","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.4049\/jimmunol.158.5.2414","article-title":"IL\u20104 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice.","volume":"158","author":"Fox C. 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