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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4296-4305. Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-08-040238. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-040238v1 109/10/4296    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 Ravet, S. Articles by Paul, P. Search for Related Content PubMed PubMed Citation Articles by Ravet, S. Articles by Paul, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 8, 2006 Accepted January 18, 2007 Distinctive NK cell receptor repertoires sustain high-level constitutive NK cell activation in HIV-exposed uninfected individuals Sophie Ravet, Daniel Scott-Algara, Elodie Bonnet, Hung Khiem Tran, Ton Tran, Ngai Nguyen, Lien Xuan Truong, Ioannis Theodorou, Francoise Barre-Sinoussi, Gianfranco Pancino, and Pascale Paul* Laboratoire Exploration NK, Laboratoire d'Hematologie, CHU Conception, Assistance Publique Hopitaux de Marseille, Marseille, France Unite de Regulation des Infections Retrovirales, Institut Pasteur, Paris, France Pasteur Institute, Ho Chi Minh City, Vietnam Binh Trieu Hospital, Ho Chi Minh City, Vietnam INSERM U543, CHU Pitie-Salpetriere, Paris, France UMR-S 608 INSERM, URF de Pharmacie Universite de la Mediterranee, Marseille, France * Corresponding author; email: pascale.paul{at}ap-hm.fr. We have previously associated high natural killer (NK) cell activity and protection against HIV-1 infection in Vietnamese exposed uninfected intravenous drug users (EUs). Considering that activating and inhibitory signals sensed by NK cell receptors regulate NK cell activation, we performed phenotypic and qRT-PCR transcript analyses of the NK cell receptor (NKR) repertoire in 25 EUs, 19 HIV+ intravenous drug users and 26 uninfected blood donors. Although NK cell activation was not linked to a unique NKR repertoire in EUs, various patterns consistent with NK cell activation were detected in EUs: high KIR3DS1/KIR3DL1 ratio associated with down-regulated KIR3DL1 transcript levels, KIR2DL3+ low affinity receptor expansion associated to group HLA-C1 ligand in 2DS2-/2DL2- EUs, enhanced NKG2C/NKG2A ratio, and increased CD69 expression. Remarkably, EUs exhibited high constitutive degranulation activity in the absence of exogenous stimulation, as shown by the CD107a assay. Furthermore, CD161 expression was increased within the CD107a+ NK cell compartment. Our results suggest that in response to viral exposition, particular genetic and/or regulated features of the NKR repertoire of EUs contribute to their high constitutive NK cell potential. This might allow NK cells to generate a more rapid and effective immune response to HIV-1, thereby contributing to prevention toward infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. N. Toka, C. Nfon, H. Dawson, and W. T. Golde Natural Killer Cell Dysfunction during Acute Infection with Foot-and-Mouth Disease Virus Clin. Vaccine Immunol., December 1, 2009; 16(12): 1738 - 1749. [Abstract] [Full Text] [PDF] M. Morvan, C. Willem, K. Gagne, N. Kerdudou, G. David, V. Sebille, G. Follea, J.-D. Bignon, and C. 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C. Maino, and L. J. Montaner Retention of viability, cytotoxicity, and response to IL-2, IL-15, or IFN-{alpha} by human NK cells after CD107a degranulation J. Leukoc. Biol., May 1, 2009; 85(5): 871 - 876. [Abstract] [Full Text] [PDF] P. Bostik, J. Kobkitjaroen, W. Tang, F. Villinger, L. E. Pereira, D. M. Little, S. T. Stephenson, M. Bouzyk, and A. A. Ansari Decreased NK Cell Frequency and Function Is Associated with Increased Risk of KIR3DL Allele Polymorphism in Simian Immunodeficiency Virus-Infected Rhesus Macaques with High Viral Loads J. Immunol., March 15, 2009; 182(6): 3638 - 3649. [Abstract] [Full Text] [PDF] A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS J. Leukoc. Biol., July 1, 2008; 84(1): 1 - 26. [Abstract] [Full Text] [PDF] A. Iannello, O. Debbeche, S. Samarani, and A. 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