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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 8, 2007 Accepted March 8, 2007 CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells Aurelie Thedrez, Claudia de Lalla, Sophie Allain, Luca Zaccagnino, Stephane Sidobre, Claudio Garavaglia, Giovanna Borsellino, Paolo Dellabona, Marc Bonneville, Emmanuel Scotet*, and Giulia Casorati U601, INSERM, Nantes, France Experimental Immunology Unit, Cancer Immunotherapy & Gene Therapy Program, H San Rafaele Scientific Institute, Milano, Italy La Jolla Institute for Allergy and Immunology, San Diego, CA, United States Neuroimmunology unit, Santa Lucia Foundation, Roma, Italy * Corresponding author; email: emmanuel.scotet{at}nantes.inserm.fr. The CD4 coreceptor is crucial in the activation of MHC class II restricted CD4+ T lymphocytes by binding the same MHC class as the TCR, and by potentiating TCR-dependent signalling. CD4 is also expressed by invariant NKT (iNKT) cells, 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 two major subsets depending on CD4 expression or not: CD4+ iNKT preferentially produce Thelper (Th)0/Th2 cytokines whereas CD4- iNKT cells produce Th1 cytokines following antigenic activation. Cytokines produced by iNKT may have immunomodulatory roles in various physiopathological 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: X. Li, T. Shiratsuchi, G. Chen, P. Dellabona, G. Casorati, R. W. Franck, and M. Tsuji Invariant TCR Rather Than CD1d Shapes the Preferential Activities of C-Glycoside Analogues Against Human Versus Murine Invariant NKT Cells J. Immunol., October 1, 2009; 183(7): 4415 - 4421. [Abstract] [Full Text] [PDF] 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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