{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:54:06Z","timestamp":1782147246842,"version":"3.54.5"},"reference-count":27,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Activation-induced cell death (AICD) is a major mechanism in the regulation of peripheral tolerance, and caspase-3 represents its major executioner. AICD impairment contributes to the persistence of autoreactive T cells, and defective AICD has been reported in autoimmune thyroiditis as well as in type 1 diabetes mellitus.<\/jats:p><jats:p>Objective: The objective of this study was to evaluate the involvement of caspase-3 in the regulation of AICD resistance in thyroid and polyendocrine autoimmunity.<\/jats:p><jats:p>Design\/Settings\/Patients\/Intervention: Caspase-3 expression was analyzed in peripheral blood lymphocytes from 26 adults (A-AT) and 25 children (Y-AT) affected by autoimmune thyroiditis and 13 individuals affected by chronic autoimmune thyroiditis plus Addison\u2019s disease [autoimmune polyendocrine syndrome-2 (APS-2)] in comparison with 32 age-matched normal control subjects (NC).<\/jats:p><jats:p>Outcome Measures: Caspase-3 mRNA expression in peripheral T cells was evaluated by quantitative real-time PCR; protein expression of both procaspase-3 and activated caspase-3 by Western blot analysis was followed by scanning densitometry.<\/jats:p><jats:p>Results: Caspase-3 mRNA expression was significantly reduced in resting lymphocytes from both A-AT (P = 0.001) and Y-AT (P = 0.016) compared with NC. After lymphocyte activation, protein levels of caspase-3 active form were significantly reduced in A-AT (P = 0.023) and Y-AT (P = 0.001) compared with NC. The APS-2 group displayed characteristics similar to the A-AT group because both caspase-3 mRNA and protein active form levels were significantly reduced compared with NC (P = 0.004 and 0.002, respectively).<\/jats:p><jats:p>Conclusion: Our data show that peripheral lymphocytes of subjects affected by thyroid autoimmunity or APS-2 show defective expression of the major executioner of AICD, thus potentially contributing to AICD resistance and to the development of autoimmunity.<\/jats:p>","DOI":"10.1210\/jc.2006-1358","type":"journal-article","created":{"date-parts":[[2006,9,13]],"date-time":"2006-09-13T02:25:13Z","timestamp":1158114313000},"page":"5064-5068","source":"Crossref","is-referenced-by-count":24,"title":["Impaired Caspase-3 Expression by Peripheral T Cells in Chronic Autoimmune Thyroiditis and in Autoimmune Polyendocrine Syndrome-2"],"prefix":"10.1210","volume":"91","author":[{"given":"Francesco","family":"Vendrame","sequence":"first","affiliation":[{"name":"Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry (F.V., V.Te., F.D.), University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Segni","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics (M.S.) 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Grassetti","sequence":"additional","affiliation":[{"name":"Clinical Sciences-Endocrinology (D.G., V.Tr.), University La Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Tellone","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry (F.V., V.Te., F.D.), University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Augello","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology (G.A., V.Tr., M.T.), Scientific Institute Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Trischitta","sequence":"additional","affiliation":[{"name":"Clinical Sciences-Endocrinology (D.G., V.Tr.), University La Sapienza, 00161 Rome, Italy"},{"name":"Unit of Endocrinology (G.A., V.Tr., M.T.), Scientific Institute Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Torlontano","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology (G.A., V.Tr., M.T.), Scientific Institute Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Dotta","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry (F.V., V.Te., F.D.), University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613471345300_R1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1034\/j.1600-065X.2003.00051.x","article-title":"Activation-induced cell death in T cells","volume":"193","author":"Green","year":"2003","journal-title":"Immunol Rev"},{"key":"2020071613471345300_R2","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0952-7915(02)00335-7","article-title":"Molecular mechanisms of activated T cell death in vivo","volume":"14","author":"Hildeman","year":"2002","journal-title":"Curr Opin Immunol"},{"key":"2020071613471345300_R3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1034\/j.1600-065X.2003.00047.x","article-title":"The role of CD95 in the regulation of peripheral T-cell apoptosis","volume":"193","author":"Krueger","year":"2003","journal-title":"Immunol Rev"},{"key":"2020071613471345300_R4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/373441a0","article-title":"Cell-autonomous Fas (CD95)\/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas","volume":"373","author":"Brunner","year":"1995","journal-title":"Nature"},{"key":"2020071613471345300_R5","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/373438a0","article-title":"Autocrine T-cell suicide mediated by APO-1\/(Fas\/CD95)","volume":"373","author":"Dhein","year":"1995","journal-title":"Nature"},{"key":"2020071613471345300_R6","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1074\/jbc.272.8.4680","article-title":"Energy metabolism during apoptosis. 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