The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer–cell subsets associated with high levels of HIV-1 viremia
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- Enrico Brunetta
- Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milano, Italy;
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- Manuela Fogli
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
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- Stefania Varchetta
- Centre for Hepatology and Infectious Diseases, Policlinico San Matteo and University of Pavia, Pavia, Italy;
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- Luisa Bozzo
- Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milano, Italy;
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- Kelly L. Hudspeth
- Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL; and
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- Emanuela Marcenaro
- Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy
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- Alessandro Moretta
- Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy
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- Domenico Mavilio
- Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milano, Italy;
書誌事項
- 公開日
- 2009-10-29
- DOI
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- 10.1182/blood-2009-06-226332
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Blood
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Blood 114 (18), 3822-3830, 2009-10-29
American Society of Hematology
