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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 (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 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 Fernandez-Malave, E. Articles by Terhorst, C. Search for Related Content PubMed PubMed Citation Articles by Fernandez-Malave, E. Articles by Terhorst, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2006 Accepted July 9, 2006 Overlapping functions of human CD3 and mouse CD3 in T cell development revealed in a humanized CD3-deficient mouse Edgar Fernandez-Malave*, Ninghai Wang, Manuel Pulgar, Wolfgang W Schamel, Balbino Alarcon, and Cox Terhorst Centro de Biologia Molecular Severo Ochoa, Madrid, Spain Beth Israel Deaconess Medical Center, Harvard Medical School Max Planck-Institut fur Immunobiologie and University of Freiburg, Germany * Corresponding author; email: efernandez{at}cbm.uam.es. 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 a 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 ndisplayed 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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