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Clin Immunol. 2008 Mar;126(3):235-42. Epub 2007 Oct 3.

Chronic innate immune activation as a cause of HIV-1 immunopathogenesis.

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  • 1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.


Human immunodeficiency virus (HIV)-1 infection causes progressive impairment of the immune system in humans, characterized by depletion of CD4 T cells and loss of T cell function. Increased markers of T cell activation and lymphoid hyperplasia suggest that chronic T cell activation persists in immunocompromised hosts, and contributes to the exhaustion of immune functions. Here we propose a revision of this hypothesis, in which we suggest that chronic activation of innate immunity may negatively affect adaptive T cell-mediated responses. We hypothesize that constant exposure of the effector cells of innate immunity to HIV results in their chronic hyperactivation, with deleterious effects on T cells. In particular, plasmacytoid dendritic cells (pDC) may be highly susceptible to HIV-induced activation due to its interaction with the cellular receptor CD4, expressed by pDC. Subsequent production of type I interferon and indoleamine 2,3-dioxygenase may exert suppressive and cytotoxic effects on T cells.

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