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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1419-1427. Prepublished online as a Blood First Edition Paper on May 20, 2004; DOI 10.1182/blood-2004-01-0201. This Article Full Text (PDF) All Versions of this Article: 2004-01-0201v1 104/5/1419    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by El Kassar, N. Articles by Gress, R. E Search for Related Content PubMed PubMed Citation Articles by El Kassar, N. Articles by Gress, R. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 20, 2004 Accepted May 2, 2004 A Dose Effect of IL-7 on Thymocyte Development Nahed El Kassar, Philip J Lucas, David B Klug, Monica Zamisch, Melinda Merchant, Catherine V Bare, Baishakhi Choudhury, Susan O Sharrow, Ellen Richie, Crystal L Mackall, and Ronald E Gress* National Cancer Institute, Experimental Immunology Branch, National Institutes of Health, Bethesda, MD, USA MD Anderson Cancer Center, Dept. of Carcinogenesis, University of Texas, Smithville, TX, USA National Cancer Institute, Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: gressr{at}exchange.nih.gov. To study IL-7 in early thymocyte development, we generated mice transgenic (Tg) for the IL-7 gene under control of the lck proximal promoter. Founder line TgA, with the lowest level of IL-7 over-expression, showed enhanced T-cell development. In contrast, in the highest over-expressing founder line, TgB, T-cell development was disturbed with a block at the earliest intra-thymic precursor stage. This was due to decreased progenitor proliferation as assessed by Ki-67 staining and in vivo BrdU incorporation. Bcl-2 was up-regulated in T-cell committed progenitors in all Tg lines, and accounted for greater numbers of DP, CD4SP 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 utilizing anti- IL-7 MAb in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype. In conclusion, at low Tg over-expression, IL-7 enhanced T-cell development by increasing thymocyte progenitor survival while at high over-expression, 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 T-cell development and has implications for IL-7 in the clinical setting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Bessette, M. L. Lang, R. A. Fava, M. Grundy, J. Heinen, L. Horne, R. Spolski, A. Al-Shami, H. C. Morse III, W. J. Leonard, et al. A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling Blood, January 1, 2008; 111(1): 344 - 350. [Abstract] [Full Text] [PDF] M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. N. Lambrecht, T. Cupedo, B. Lowenberg, J. J. Cornelissen, and E. Braakman Keratinocyte Growth Factor Induces Expansion of Murine Peripheral CD4+Foxp3+ Regulatory T Cells and Increases Their Thymic Output J. Immunol., December 1, 2007; 179(11): 7424 - 7430. [Abstract] [Full Text] [PDF] K. Clise-Dwyer, G. E. Huston, A. L. Buck, D. K. Duso, and S. L. 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