In vitro human immunodeficiency virus eradication by autologous CD8(+) T cells expanded with inactivated-virus-pulsed dendritic cells.
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.
Lu
W
W
Laboratory of Molecular Oncology and Virology, Necker Faculty of Medicine at Saints-Pères Biomedical Center, René Descartes University, Paris, France. louis.weilu@biomedicale.univ-paris5.fr
Andrieu
J M
JM
D019380:Anti-HIV Agents / Q000276:immunology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male
D019380:Anti-HIV Agents