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However, whether ongoing Dll4\u2010Notch signaling is required for T\u2010cell development in the adult thymus is unknown. The use of anti\u2010Dll4 Abs allowed us to confirm and expand previous studies by examining the kinetics and the reversibility of Dll4\u2010Notch signaling blockade in T\u2010cell development in adult mice. We found that anti\u2010Dll4 treatment reduced thymic cellularity after 7 days, as a consequence of a developmental delay in T\u2010cell maturation at the pro\u2010T\u2010cell double negative 1 (CD4<jats:sup>\u2212<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup>c\u2010kit<jats:sup>+<\/jats:sup>CD44<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>) stage, leading to decreased numbers of immature double\u2010positive (CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>) T cells without affecting the frequency of mature single positive CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> thymocytes, while promoting alternative thymic B\u2010cell expansion. This cellular phenotype was similarly observed in both young adult and aged mice (&gt;1.5 years), extending our understanding of the ongoing role for Dll4\u2010Notch signaling during T\u2010cell development in the adult thymus. Finally, after cessation of Dll4 Ab treatment, thymic cellularity and thymocyte subset ratios returned to normal levels, indicating reversibility of this phenotype in both adult and aged mice, which has important implications for potential clinical use of Dll4\u2010Notch inhibitors.<\/jats:p>","DOI":"10.1002\/eji.201041343","type":"journal-article","created":{"date-parts":[[2011,5,20]],"date-time":"2011-05-20T06:56:59Z","timestamp":1305874619000},"page":"2207-2216","source":"Crossref","is-referenced-by-count":22,"title":["Ongoing Dll4\u2010Notch signaling is required for T\u2010cell homeostasis in the adult thymus"],"prefix":"10.1002","volume":"41","author":[{"given":"Fabienne","family":"Billiard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica 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