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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4165-4172. Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-06-2484. This Article Full Text (PDF) All Versions of this Article: 2004-06-2484v1 104/13/4165    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 Munitic, I. Articles by Ashwell, J. D Search for Related Content PubMed PubMed Citation Articles by Munitic, I. Articles by Ashwell, J. D Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 30, 2004 Accepted August 11, 2004 Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis Ivana Munitic, Joy A Williams, Yili Yang, Bei Dong, Philip J Lucas, Nahed El Kassar, Ronald E Gress, and Jonathan D Ashwell* Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA Experimental Immunology Branch, NCI, Bethesda, MD, USA * Corresponding author; email: jda{at}pop.nci.nih.gov. IL-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on DN cells, absent on DP cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage specific IL-7R chain (IL-7R) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7R Tg on negative selection. Surprisingly, however, although the thymi of IL-7R Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DN cells, increased DN apoptosis, and decreased DN cell number. Therefore, the downregulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: IL-7: a limited resource during thymopoiesis Thomas R. Malek Blood 2004 104: 3842. [Full Text] [PDF] This article has been cited by other articles: S. Gonzalez-Garcia, M. Garcia-Peydro, E. Martin-Gayo, E. Ballestar, M. Esteller, R. Bornstein, J. L. de la Pompa, A. A. Ferrando, and M. L. Toribio CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia J. Exp. Med., April 13, 2009; 206(4): 779 - 791. [Abstract] [Full Text] [PDF] M. Lavanya, S. Kinet, A. Montel-Hagen, C. Mongellaz, J.-L. Battini, M. Sitbon, and N. Taylor Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement J. Immunol., July 15, 2008; 181(2): 891 - 898. [Abstract] [Full Text] [PDF] J. S. Haring, X. Jing, J. Bollenbacher-Reilley, H.-H. Xue, W. J. Leonard, and J. T. 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Malek Selective Availability of IL-2 Is a Major Determinant Controlling the Production of CD4+CD25+Foxp3+ T Regulatory Cells J. Immunol., October 15, 2006; 177(8): 5115 - 5121. [Abstract] [Full Text] [PDF] T. J. Fry IL-7 comes of age Blood, April 1, 2006; 107(7): 2587 - 2588. [Full Text] [PDF] Q. Yu, J.-H. Park, L. L. Doan, B. Erman, L. Feigenbaum, and A. Singer Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection J. Exp. Med., January 23, 2006; 203(1): 165 - 175. [Abstract] [Full Text] [PDF] C. G. Radu, D. Cheng, A. Nijagal, M. Riedinger, J. McLaughlin, L. V. Yang, J. Johnson, and O. N. Witte Normal Immune Development and Glucocorticoid-Induced Thymocyte Apoptosis in Mice Deficient for the T-Cell Death-Associated Gene 8 Receptor Mol. Cell. Biol., January 15, 2006; 26(2): 668 - 677. [Abstract] [Full Text] [PDF] D. Penkov, P. Di Rosa, L. Fernandez Diaz, V. Basso, E. Ferretti, F. Grassi, A. Mondino, and F. Blasi Involvement of Prep1 in the {alpha}{beta} T-Cell Receptor T-Lymphocytic Potential of Hematopoietic Precursors Mol. Cell. Biol., December 15, 2005; 25(24): 10768 - 10781. [Abstract] [Full Text] [PDF] T. J. Fry and C. L. Mackall The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance J. Immunol., June 1, 2005; 174(11): 6571 - 6576. [Abstract] [Full Text] [PDF]

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