{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:41:59Z","timestamp":1775043719854,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>When granulomatous experimental autoimmune thyroiditis (G-EAT) was induced in CBA\/J or DBA\/1 mice, thyroid lesions resolved in less severe (3+) G-EAT in wild-type mice or severe (5+) G-EAT in IFN-\u03b3\u2212\/\u2212 mice, but progressed to fibrosis in 5+ G-EAT in wild-type mice. To define the mechanisms leading to these distinct outcomes, the expression of inflammatory and apoptotic molecules and infiltrating cells was evaluated using immunohistochemistry, RT-PCR, and confocal microscopy. The ratio of CD4+\/CD8+ T cells in thyroid infiltrates was one factor that predicted G-EAT outcome. CD4+ T cells outnumbered CD8+ T cells when lesions progressed to fibrosis, while CD8+ T cells outnumbered CD4+ T cells in thyroids that resolved. Fas, Fas ligand, FLIP, TNF-\u03b1, inducible NO synthase, TGF-\u03b2, and IFN-\u03b3 were highly expressed by infiltrating cells when G-EAT progressed to fibrosis. The expression of active caspase-3 was low, possibly contributing to the persistence of CD4+ T cells in fibrosis. In contrast, FLIP was mainly expressed by thyrocytes in resolving G-EAT, the expression of active caspase-3 was high, and resolution correlated with apoptosis of infiltrating cells. There was also relatively less expression of TGF-\u03b2, IFN-\u03b3, TNF-\u03b1, and inducible NO synthase and higher expression of IL-10 in resolving G-EAT than in G-EAT that progressed to fibrosis. These differences were particularly striking when comparing IFN-\u03b3\u2212\/\u2212 vs wild-type mice. These results suggest that several opposing biological mechanisms contribute to the outcome of an ongoing autoimmune response. These include differential expression of pro- and antiapoptotic molecules, cytokines, and the ratio of CD4+ vs CD8+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.171.11.6236","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:32:01Z","timestamp":1398029521000},"page":"6236-6243","source":"Crossref","is-referenced-by-count":30,"title":["Mechanisms of Spontaneous Resolution versus Fibrosis in Granulomatous Experimental Autoimmune Thyroiditis"],"prefix":"10.1093","volume":"171","author":[{"given":"Kemin","family":"Chen","sequence":"first","affiliation":[{"name":"Internal Medicine, University of Missouri School of Medicine , Columbia, MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhong","family":"Wei","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Missouri School of Medicine , Columbia, MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon C","family":"Sharp","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Missouri School of Medicine , Columbia, MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Braley-Mullen","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Missouri School of Medicine , Columbia, MO 65212"},{"name":"Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia, MO 65212"},{"name":"Veterans Affairs Research Service , Columbia, MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,12,1]]},"reference":[{"key":"2026020210244137000_R1","first-page":"535","volume-title":"Int. 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