Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8+ T cell immunity

Maturation of dendritic cells (DC) to enhance their capacity to activate T cell immunity to HIV‐1 is a key step in immunotherapy of HIV‐1 infection with DC. We compared maturation of DC derived from HIV‐1‐uninfected subjects and infected subjects on antiretroviral therapy (ART) or ART naïve by CD40 ligand (CD40L) and combinations of TLR3 ligand polyinosinic:polycytidylic acid [poly(I:C)] and inflammatory cytokines IFN‐γ, IFN‐α, IL‐1β, and TNF‐α. The greatest levels of virus‐specific IFN‐γ production by CD8+ T cells were stimulated by DC treated with CD40L, followed by DC treated with the poly(I:C)‐cytokine combination. The highest levels of IL‐12p70 were produced by DC treated with CD40L + IFN‐γ, followed by CD40L and the poly(I:C)‐cytokine combination. Neutralization of IL‐12p70 indicated that it was only partially involved in direct enhancement of antiviral CD8+ T cell activity. DC stimulation of antiviral CD8+ T cell reactivity was enhanced by activated CD4+ T cells at low concentrations but was suppressed at higher CD4+ T cell concentrations. Maturation of DC with CD40L obviated the need for CD4+ T cell help and overcame this suppressive activity. Finally, we showed that DC from HIV‐1‐infected subjects on ART, which were treated with the poly(I:C)‐cytokine combination, retained the capacity to produce IL‐12p70 and activate anti‐HIV‐1 CD8+ T cell responses after restimulation with CD40L, with or without IFN‐γ. Thus, DC from HIV‐1‐infected subjects can be engineered with CD40L or a poly(I:C)‐cytokine combination for enhancing CD8+ T cell responses to HIV‐1, which has potential applications in HIV‐1 immunotherapy.