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This was due to decreased progenitor proliferation as assessed by Ki-67 staining and in vivo bromodeoxyuridine (BrdU) incorporation. Bcl-2 was up-regulated in T-cell\u2013committed progenitors in all Tg lines, and accounted for greater numbers of double positive (DP), CD4 single positive (SP), and CD8SP thymocytes in TgA mice where, in contrast to TgB mice, thymocyte progenitor proliferation was normal. Mixed marrow chimeras using TgB+ and congenic mice as donors, and experiments using anti\u2013IL-7 monoclonal antibody (MAb) in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype. In conclusion, at low Tg overexpression, IL-7 enhanced \u03b1\u03b2 T-cell development by increasing thymocyte progenitor survival, while at high overexpression IL-7 reduces their proliferation, inducing a dramatic block in DP production. These results show for the first time in vivo a dose effect of IL-7 on \u03b1\u03b2 T-cell development and have implications for IL-7 in the clinical setting.<\/jats:p>","DOI":"10.1182\/blood-2004-01-0201","type":"journal-article","created":{"date-parts":[[2004,5,25]],"date-time":"2004-05-25T00:13:27Z","timestamp":1085444007000},"page":"1419-1427","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":59,"title":["A dose effect of IL-7 on thymocyte development"],"prefix":"10.1182","volume":"104","author":[{"given":"Nahed","family":"El Kassar","sequence":"first","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Klug","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zamisch","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Merchant","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine V.","family":"Bare","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baishakhi","family":"Choudhury","sequence":"additional","affiliation":[{"name":"From the Experimental Immunology Branch and the Pediatric Oncology Branch, National Cancer Institute (NCI), Bethesda, MD; and the University of Texas, M. D. 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