Nat Immunol. 2007 Nov;8(11):1246-54. Epub 2007 Sep 30.

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

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Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. dkaufmann@partners.org

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.

PMID:: 17906628; [PubMed - indexed for MEDLINE]

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