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Blood, 1 July 2007, Vol. 110, No. 1, pp. 251-258. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2007-01-066217. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-01-066217v1 110/1/251    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 Thedrez, A. Articles by Casorati, G. Search for Related Content PubMed PubMed Citation Articles by Thedrez, A. Articles by Casorati, G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells Aurelie Thedrez1, Claudia de Lalla2, Sophie Allain1, Luca Zaccagnino2, Stephane Sidobre3, Claudio Garavaglia2, Giovanna Borsellino4, Paolo Dellabona2, Marc Bonneville1, Emmanuel Scotet1, and Giulia Casorati2 1 Institute Nationale Scientifique et Recherche Medicale, Nantes, France; Université de Nantes, France; 2 Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, H San Raffaele Scientific Institute, Milan, Italy; 3 La Jolla Institute for Allergy and Immunology, San Diego, CA; 4 Neuroimmunology unit, Santa Lucia Foundation, Rome, Italy The CD4 coreceptor is crucial in the activation of major histocompatibility complex (MHC) class II restricted CD4 + T lymphocytes by binding the same MHC class as the T-cell receptor (TCR) and by potentiating TCR-dependent signaling. CD4 is also expressed by invariant natural killer T cells (iNKT), which recognize natural and synthetic lipid antigens, such as -galactosyl ceramide (-GalCer), in association with the MHC class I–like CD1d molecule. Human iNKT cells can be divided into 2 major subsets depending on CD4 expression: CD4 + iNKT preferentially produce T-helper (Th)0/Th2 cytokines, whereas CD4– iNKT cells produce Th1 cytokines after antigenic activation. Cytokines produced by iNKT may have immunomodulatory roles in various physiopathologic contexts, but their mode of regulation by iNKT cells remains ill-defined. Using blocking reagents neutralizing CD4 binding, experimental systems where MHC class II molecules are absent and recombinant -GalCer/CD1d complexes, we show that CD4 potentiates human iNKT cell activation by engaging CD1d molecules. These results indicate that the CD4 coreceptors may contribute to the fine tuning of iNKT cells reactivity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Akbari, P. Stock, E. H. Meyer, G. J. Freeman, A. H. Sharpe, D. T. Umetsu, and R. H. DeKruyff ICOS/ICOSL Interaction Is Required for CD4+ Invariant NKT Cell Function and Homeostatic Survival J. Immunol., April 15, 2008; 180(8): 5448 - 5456. [Abstract] [Full Text] [PDF] X. Chen, X. Wang, G. S. Besra, and J. E. Gumperz Modulation of CD1d-restricted NKT cell responses by CD4 J. Leukoc. Biol., December 1, 2007; 82(6): 1455 - 1465. [Abstract] [Full Text] [PDF]

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