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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3822-3830. Prepublished online as a Blood First Edition Paper on August 26, 2009; DOI 10.1182/blood-2009-06-226332. This Article Full Text Full Text (PDF) Supplemental Methods All Versions of this Article: blood-2009-06-226332v1 114/18/3822    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 CrossRef Google Scholar Articles by Brunetta, E. Articles by Mavilio, D. PubMed PubMed Citation Articles by Brunetta, E. Articles by Mavilio, D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer–cell subsets associated with high levels of HIV-1 viremia Enrico Brunetta1,2, Manuela Fogli2, Stefania Varchetta3, Luisa Bozzo1, Kelly L. Hudspeth4, Emanuela Marcenaro5, Alessandro Moretta5, and Domenico Mavilio1 1 Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milano, Italy; 2 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; 3 Centre for Hepatology and Infectious Diseases, Policlinico San Matteo and University of Pavia, Pavia, Italy; 4 Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL; and 5 Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy HIV-1 has developed several strategies to evade natural killer (NK)–cell antiviral functions. One of these mechanisms is the HIV-1–induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1–infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid–binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7–/CD56+) or chronic (Siglec-7–/CD56–) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone antiretroviral therapy. High frequencies of Siglec-7–/CD56+ and Siglec-7–/CD56– pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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