A delicate balance between immunostimulatory and immunosuppressive signals mediated by dendritic cells (DC) and other antigen-presenting cells (APC) regulates the strength and efficacy of anti-viral T cell responses. The human immunodeficiency virus (HIV) is a potent activator of plasmacytoid DC (pDC). Chronic pDC activation by HIV promotes the pathogenesis of the acquired human immunodeficiency syndrome (AIDS). Cholesterol is pivotal in maintaining HIV envelope integrity and allowing HIV-cell interaction. By depleting envelope-associated cholesterol to different degrees, we generated virions with reduced ability to activate pDC. We found that APC activation was dissociated from the induction of type I interferon (IFN-α/β) and indoleamine 2,3-dioxygenase-mediated immunosuppression in vitro. Extensive cholesterol withdrawal, resulting in partial protein and RNA loss from the virions, rendered HIV a more powerful recall immunogen for stimulating memory CD8 T cell responses in HIV-exposed uninfected individuals. These enhanced responses were dependent on the inability of cholesterol-depleted HIV to induce IFN-α/β.
- Submitted March 23, 2011.
- Accepted September 8, 2011.
- Copyright © 2005 American Society of Hematology