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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3420-3427. Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-03-010850. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-010850v1 108/10/3420    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 Fernández-Malavé, E. Articles by Terhorst, C. Search for Related Content PubMed PubMed Citation Articles by Fernández-Malavé, E. Articles by Terhorst, C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Overlapping functions of human CD3 and mouse CD3 in T-cell development revealed in a humanized CD3-deficient mouse Edgar Fernández-Malavé, Ninghai Wang, Manuel Pulgar, Wolfgang W. A. Schamel, Balbino Alarcón, and Cox Terhorst From the Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain; the Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Max Planck-Institut für Immunobiologie, Freiburg, Germany; and the University of Freiburg, Germany. Humans lacking the CD3 subunit of the pre-TCR and TCR complexes exhibit a mild T lymphopenia, but have normal T cells. By contrast, CD3-deficient mice are almost devoid of mature T cells due to an early block of intrathymic development at the CD4–CD8– double-negative (DN) stage. This suggests that in humans but not in mice, the highly related CD3 chain replaces CD3 during T-cell development. To determine whether human CD3 (hCD3) functions in a similar manner in the mouse in the absence of CD3, we introduced an hCD3 transgene in mice that were deficient for both CD3 and CD3, in which thymocyte development is completely arrested at the DN stage. Expression of hCD3 efficiently supported pre-TCR–mediated progression from the DN to the CD4+CD8+ double-positive (DP) stage. However, TCR-mediated positive and negative thymocyte selection was less efficient than in wild-type mice, which correlated with a marked attenuation of TCR-mediated signaling. Of note, murine CD3-deficient TCR complexes that had incorporated hCD3 displayed abnormalities in structural stability resembling those of T cells from CD3-deficient humans. Taken together, these data demonstrate that CD3 and CD3 play a different role in humans and mice in pre-TCR and TCR function during T-cell development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. M. Siegers, M. Swamy, E. Fernandez-Malave, S. Minguet, S. Rathmann, A. C. Guardo, V. Perez-Flores, J. R. Regueiro, B. Alarcon, P. Fisch, et al. Different composition of the human and the mouse {gamma}{delta} T cell receptor explains different phenotypes of CD3{gamma} and CD3{delta} immunodeficiencies J. Exp. Med., October 29, 2007; 204(11): 2537 - 2544. [Abstract] [Full Text] [PDF] M. Touma, Z.-Y. J. Sun, L. K. Clayton, W. E. Marissen, A. M. Kruisbeek, G. Wagner, and E. L. Reinherz Importance of the CD3{gamma} Ectodomain Terminal beta-Strand and Membrane Proximal Stalk in Thymic Development and Receptor Assembly J. Immunol., March 15, 2007; 178(6): 3668 - 3679. [Abstract] [Full Text] [PDF] M. J. Recio, M. A. Moreno-Pelayo, S. S. Kilic, A. C. Guardo, O. Sanal, L. M. Allende, V. Perez-Flores, A. Mencia, S. Modamio-Hoybjor, E. Seoane, et al. Differential Biological Role of CD3 Chains Revealed by Human Immunodeficiencies J. Immunol., February 15, 2007; 178(4): 2556 - 2564. [Abstract] [Full Text] [PDF]

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