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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 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 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 Ravet, S. Articles by Paul, P. Search for Related Content PubMed PubMed Citation Articles by Ravet, S. Articles by Paul, P. Related Collections Clinical Trials and Observations Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals Sophie Ravet1,2, Daniel Scott-Algara3, Elodie Bonnet1, Hung Khiem Tran4, Ton Tran4,6, Ngai Nguyen5, Lien Xuan Truong4, Ioannis Theodorou6, Françoise Barré-Sinoussi3, Gianfranco Pancino3, and Pascale Paul1,2 1 Laboratoire Exploration NK, Laboratoire d'Hématologie, Centre Hospitalo-Universitaire (CHU) Conception, Assistance Publique Hôpitaux de Marseille, France; 2 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité mixte de recherche (UMR)–S 608, Unité de Formation et de Recherche (URF) de Pharmacie Université de la Méditerranée, Marseille, France; 3 Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris France; 4 Pasteur Institute, Ho Chi Minh City, Vietnam; 5 INSERM U543, CHU Pitié-Salpêtrière, Paris, France; 6 Binh Trieu Hospital, Ho Chi Minh City, Vietnam We have previously associated high natural killer (NK)–cell activity and protection against HIV-1 infection in Vietnamese exposed uninfected intravascular drug users (EUs). Considering that activating and inhibitory signals sensed by NK-cell receptors regulate NK-cell activation, we performed phenotypic and quantitative reverse transcription-polymerase chain reaction (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 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: 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. Ahmad Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49. [Abstract] [Full Text] [PDF]

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