NKG2D expression on HIV-specific CD8+ T cells is reduced in viremic HIV-1-infected patients but maintained in HIV controllers

1INSERM, U1012, Le Kremlin Bicêtre, France 2Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France 3INSERM U986, Hôpital St-Vincent de Paul, Paris, France 4Université Paris-Sud, U1012, Le Kremlin Bicêtre, France 5AP-HP, Service de Médecine Interne et Maladies Infectieuses, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2012; 62(1). DOI: 10.1097/QAI.0b013e318274579f
Source: PubMed


NKG2D mediates an important co-stimulatory pathway in CD8 T cells. In HIV infection, we found that NKG2D expression on both total and HIV-specific CD8 T cells was significantly lower in viremic patients than in HIV controllers. Antiretroviral therapy partially restored NKG2D expression on HIV-specific CD8 T cells. We observed a negative correlation between the respective expression levels of CD38 and NKG2D on total CD8 and HIV-specific CD8 T cells. The maintenance of NKG2D expression on CD8 T cells in HIV controllers may contribute to better cell function.

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Available from: Asier Sáez-Cirión, Apr 14, 2014
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    ABSTRACT: Human immunodeficiency virus (HIV) infection in humans does not always lead to AIDS. Rare HIV-1 infected individuals known as HIV Controllers do not show signs of disease progression in the long term and spontaneously control HIV replication to very low levels in the absence of therapy. Simian species that are naturally infected by SIV in the wild provide an apparently radically different model of resistance to AIDS, as the plasma viral load remains persistently high in these species without obvious pathogenic consequences. Infections in HIV Controllers and SIV natural hosts differ in several major points, such the strength and avidity of the antiviral T cell response, which are remarkably high in Controllers. However, close examination of the human and simian models also reveals common threads, highlighting key elements involved in resisting AIDS: these include contained levels of chronic immune activation, a downregulation of the interferon response, a low viral load in lymph nodes, and a relative protection from infection of certain CD4+ T cell subsets, including central memory cells and possibly follicular helper T cells. Studies of non-pathogenic HIV and SIV infections thus point to the importance of protecting the lymphoid environment from massive infection to avoid the triggering of a deleterious chronic immune activation, a notion that may inform the development of immunotherapeutic and vaccinal approaches against HIV.
    Natural Hosts of SIV: Implications in AIDS, 1st edited by Ansari A. A. and Silvestri G., 07/2014: pages 287-352; Academic Press, Elsevier., ISBN: 978-0-12-404734-1