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Upregulation of CTLA-4 by HIV-specific CD4(+) T cells correlates with disease progression and defines a reversible immune dysfunction

  1. Author:
    Kaufmann, D. E.
    Kavanagh, D. G.
    Pereyra, F.
    Zaunders, J. J.
    Mackey, E. W.
    Miura, T.
    Palmer, S.
    Brockman, M.
    Rathod, A.
    Piechocka-Trocha, A.
    Baker, B.
    Zhu, B.
    Le Gall, S.
    Waring, M. T.
    Ahern, R.
    Moss, K.
    Kelleher, A. D.
    Coffin, J. M.
    Freeman, G. J.
    Rosenberg, E. S.
    Walker, B. D.

  2. Author Address

    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. St Vincents Hosp, Ctr Immunol, Darlinghurst, NSW 2010, Australia. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA.;Kaufmann, DE, Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA.;dkaufmann@partners.org
    1. Year: 2007
    2. Date: Nov
  2. Journal: Nature Immunology
    1. 8
    2. 11
    3. Pages: 1246-1254
  4. Type of Article: Article
  5. ISSN: 1529-2908
  1. Abstract:

    In progressive viral infection, antiviral T cell function is impaired by poorly understood mechanisms. Here we report that the inhibitory immunoregulatory receptor CTLA-4 was selectively upregulated in human immunodeficiency virus (HIV)-specific CD4(+) T cells but not CD8(+) T cells in all categories of HIV-infected subjects evaluated, with the exception of rare people able to control viremia in the absence of antiretroviral therapy. CTLA-4 expression correlated positively with disease progression and negatively with the capacity of CD4(+) T cells to produce interleukin 2 in response to viral antigen. Most HIV-specific CD4(+) T cells coexpressed CTLA-4 and another inhibitory immunoregulatory receptor, PD-1. In vitro blockade of CTLA-4 augmented HIV-specific CD4(+) T cell function. These data, indicating a reversible immunoregulatory pathway selectively associated with CD4(+) T cell dysfunction, provide a potential target for immunotherapy in HIV-infected patients.

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External Sources

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  2. DOI: 10.1038/ni1515
  3. View record in Web of Science®
  4. WOS: 000250338900017

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