Differential impact of late-stage HIV-1 infection on in vitro and in vivo maturation of myeloid dendritic cells

Abstract

The functional and phenotypic maturation of myeloid dendritic cells (DCs), circulating and monocyte-derived, from subjects at different stages of HIV-1 infection was evaluated. The results showed that the capacity of circulating DCs was significantly impaired in subjects with CD4+ T cell counts of <200/microL, correlated with the potential of CD40 ligand expression on CD4+ T cells (R = 0.84; P = 0.002), and improved with successful antiretroviral therapy. However, the function and phenotype of monocyte-derived DCs generated by in vitro culture from subjects at any stage of HIV-1 infection were similar to those in uninfected healthy subjects. Our findings suggest that although the potential of myeloid DC precursors to achieve full maturation is preserved in subjects with late-stage HIV-1 infection, in vivo maturation of myeloid DCs was impaired in these subjects, which may be due to decreased potential of CD40 ligand expression on CD4+ T cells. That myeloid DCs fail to achieve full maturation in vivo in late-stage HIV-1 infection may contribute to the failure to induce effective cellular immunity against HIV-1 and opportunistic pathogens.