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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 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 Citation Map 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 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. To study interleukin-7 (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 overexpression, showed enhanced T-cell development. In contrast, in the highest overexpressing founder line, TgB, T-cell development was disturbed with a block at the earliest intrathymic precursor stage. 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–committed 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–IL-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 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 T-cell development and have 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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Erman, J.-H. Park, L. Feigenbaum, and A. Singer IL-7 Receptor Signals Inhibit Expression of Transcription Factors TCF-1, LEF-1, and ROR{gamma}t: Impact on Thymocyte Development J. Exp. Med., September 20, 2004; 200(6): 797 - 803. [Abstract] [Full Text] [PDF]

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