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Journal of Virology, October 2001, p. 8949-8956, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.8949-8956.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Human Immunodeficiency Virus Eradication by Autologous CD8+ T Cells Expanded with Inactivated-Virus-Pulsed Dendritic Cells

Wei Lu* and Jean-Marie Andrieu

Laboratory of Molecular Oncology and Virology, Necker Faculty of Medicine at Saints-Pères Biomedical Center, René Descartes University, Paris, France

Received 21 March 2001/Accepted 13 June 2001

Despite significant immune recovery with potent highly active antiretroviral therapy (HAART), eradication of human immunodeficiency virus (HIV) from the bodies of infected individuals represents a challenge. We hypothesized that an inadequate or inappropriate signal in virus-specific antigen presentation might contribute to the persistent failure to mount efficient anti-HIV immunity in most HIV-infected individuals. Here, we conducted an in vitro study with untreated (n = 10) and HAART-treated (n = 20) HIV type 1 (HIV-1) patients which showed that pulsing of monocyte-derived dendritic cells (DC) with aldrithiol-2-inactivated autologous virus resulted in the expansion of virus-specific CD8+ T cells which were capable of killing HIV-1-infected cells and eradicating the virus from cultured patient peripheral blood mononuclear cells independently of the disease stages and HAART response statuses of the patients. This in vitro anti-HIV effect was further enhanced by the HIV protease inhibitor indinavir (at a nonantiviral concentration), which has been shown previously to be able to up-regulate directly patient T-cell proliferation following immune stimulation. However, following a 2-day treatment with culture supernatant derived from immune-activated T cells (which mimics an in vivo environment of HIV-disseminated and immune-activated lymphoid tissues), DC lost their capacity to present de novo inactivated-virus-derived antigens. These findings provide important information for understanding the establishment of chronic HIV infection and indicate a perspective for clinical use of DC-based therapeutic vaccines against HIV.

* Corresponding author. Mailing address: Laboratoire d'Oncologie et Virologie Moléculaires, Centre Biomedical des Saints-Pères, Université René Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France. Phone: 33-1 42 60 19 22. Fax: 33-1 42 60 19 88. E-mail: louis.weilu{at}biomedicale.univ-paris5.fr.

Journal of Virology, October 2001, p. 8949-8956, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.8949-8956.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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