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* Biomedical Primate Research Centre, Rijswijk, The Netherlands;
Centro di Eccellenza per la Ricerca Biomedica, Genoa, Italy;
Dipartimento di Medicina Sperimentale, Università di Genova, Genoa, Italy;
Istituto Scientifico Giannina Gaslini, Genoa, Italy;
¶ Dipartimento di Oncologia Biologia e Ginecologia, Università di Genova, Genoa, Italy;
|| Istituto Nazionale per la Ricerca sul Cancro e Centro di Biotechnologie Avanzate, Genoa Italy; and
# Dipartimento di Medicina Interna, Università di Genova, Genoa, Italy
HIV-1 infection in chimpanzees, the closest human relative, rarely leads to disease progression. NK cells contribute to the shaping of adaptive immune responses in humans and show perturbed phenotype and function during HIV-1 infection. In this study, we provide full phenotypic, molecular, and functional characterization for triggering molecules (NKp46, NKp30 NKp80, and NKG2D) on Pan troglodytes NK cells. We demonstrate that, in this AIDS-resistant species, relevant differences to human NK cells involve NKp80 and particularly NKp30, which is primarily involved in NK-dendritic cell interactions. Resting peripheral chimpanzee NK cells have low or absent NKp30 molecule expression due to posttranscriptional regulation and increase its levels upon in vitro activation. Following long-standing HIV-1 infection, peripheral NK cells in chimpanzees have conserved triggering receptor expression and display moderate phenotypic and functional decreases only once activated and cultured in vitro. These data suggest that one of the keys to successful lentivirus control may reside in part in a different regulation of NK cell-triggering receptor expression.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the National Institutes of Health (POI AI48225), Istituto Superiore di Sanità (Programma Nazionale AIDS 40F.55, Italian Concerted Action for AIDS Vaccine, Accordi di Collaborazione Scientifica 40D61, 45D/1.13, 45F12), Ministero della Salute (RF 2002/149), Associazione Italiana per la Ricerca sul Cancro, and Ministero dellIstruzione dellUniversità e della Ricerca.
2 E.R. and S.M. equally contributed to this work.
3 Current address: National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
4 Address correspondence and reprint requests to Dr. Andrea De Maria, Department of Internal Medicine, University of Genoa, Largo R. Benzi 10, 16132 Genoa, Italy. E-mail address: de-maria{at}unige.it
5 Abbreviations used in this paper: DC, dendritic cell; DNAM, DNAX accessory molecule; HPV, human papillomavirus; LTNP, long-term nonprogressive; MFI, mean fluorescence intensity; NCR, natural cytotoxicity receptor; TM, transmembrane.
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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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