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 Blood, 29 October 2009, Vol. 114, No. 18, pp. 3854-3863.
Prepublished online as a Blood First Edition Paper on August 18, 2009; DOI 10.1182/blood-2009-04-217927.

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IMMUNOBIOLOGY

Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients

Georg Stary1, Irene Klein1, Sabine Kohlhofer1, Frieder Koszik1, Thomas Scherzer2, Leonhard Müllauer3, Heribert Quendler4, Norbert Kohrgruber1,*, and Georg Stingl1,*

1 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, 2 Department of Internal Medicine III, Division of Gastroenterology and Hepatology, and 3 Department of Clinical Pathology, Medical University of Vienna, Vienna; and 4 Department of Biotechnology, Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Vienna, Austria

Artificial Toll-like receptor 7/8 (TLR7/8) ligands can endow plasmacytoid dendritic cells (pDCs) with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–dependent lytic properties. Keeping in mind that ssRNA serves as natural TLR7/8 ligand, we searched for TRAIL-expressing cells in persons infected with HIV and identified TRAIL+ pDCs in HIV-1 viremic persons, but not in nonviremic and healthy persons. TRAIL expression on pDCs was directly correlated with individual viral loads. Conversely, HIV-1 viremia was found to be associated with the up-regulation of the apoptosis-transmitting receptor TRAIL R1 on activated CD4+ T cells. As a consequence, the latter became susceptible to TRAIL-dependent pDC-mediated killing. In contrast, initiation of antiretroviral therapy led to the up-regulation of apoptosis-inhibiting TRAIL R4 on CD4+ T cells, which subsequently became resistant against pDC-mediated cellular injury. Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection.


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Related Article in Blood Online:

HIV infection: TRAILing the killers
Andrea Cerutti
Blood 2009 114: 3723-3724. [Full Text] [PDF]



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A. Cerutti
HIV infection: TRAILing the killers
Blood, October 29, 2009; 114(18): 3723 - 3724.
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