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However, the potential mechanisms for these changes have not been fully elucidated. The current study used the <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n mouse model of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> to assess deficiencies in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell development and possible molecular alterations. <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n mice exhibited premature thymic involution and a threefold to fourfold decrease in the number and proportion of immature, double\u2010negative thymocyte progenitors. In addition, there were twofold fewer double\u2010positive and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 single\u2010positive thymocytes in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n thymuses. Reflecting this deficient thymic function, there were fewer naive <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells in the spleen and polyclonal stimulation of peripheral <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells exhibited a marked reduction in proliferation, suggesting a senescent phenotype. In contrast, <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\u2010cell progenitors were unchanged in the bone marrow of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n mice, but in the spleen, there were decreased transitional and follicular <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> cells and these cells proliferated less upon antigen receptor stimulus but not in response to lipopolysaccharide. As a potential mechanism for diminished thymic function, immature thymocyte populations expressed diminished levels of the cytokine receptor interleukin\u20107<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u03b1, which was associated with decreased proliferation and increased apoptosis. Increased oxidative stress and inhibition of the <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch pathway were identified as possible mediators of decreased interleukin\u20107<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u03b1 expression in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n mice. The data suggest that immature thymocyte defects underlie immune dysfunction in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> and that increased oxidative stress and reduced cytokine signalling may alter lymphocyte development in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>s65<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>n mice.<\/jats:p>","DOI":"10.1111\/imm.12092","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T05:54:24Z","timestamp":1361512464000},"page":"447-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Defective thymic progenitor development and mature <scp>T<\/scp>\u2010cell responses in a mouse model for <scp>D<\/scp>own syndrome"],"prefix":"10.1111","volume":"139","author":[{"given":"Laureanne P. 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