There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However， the effects of aging on DC responses to bacterial lipopolysaccharide (LPS)， the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s， mDC2s， plasmacytoid (p)DCs， and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation. All elderly DC su... More
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However， the effects of aging on DC responses to bacterial lipopolysaccharide (LPS)， the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s， mDC2s， plasmacytoid (p)DCs， and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation. All elderly DC subsets demonstrated comparable up-regulation of co-stimulatory molecules (CD40， CD80 and/or CD86)， intracellular pro-inflammatory cytokine levels (IFN-γ， tumour necrosis factor (TNF)-α， IL-6 and/or IL-12)， and/or secreted cytokine levels (IFN-α， IFN-γ， TNF-α， and IL-12) to their younger counterparts. Furthermore， elderly-derived LPS/IFN-γ or CD40L-activated MoDCs induced similar or increased levels of CD8+ and CD4+ T cell proliferation， and similar T cell functional phenotypes， to their younger counterparts. However， elderly LPS/IFN-γ-activated MoDCs were unreliable in their ability to up-regulate chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and IL-6 secretion， implying an inability to dependably induce an inflammatory response. A key age-related difference was that， unlike young-derived MoDCs that completely lost their ability to process antigen， elderly-derived MoDCs maintained their antigen processing ability after LPS/IFN-γ maturation， measured using the DQ-ovalbumin assay; this response implies incomplete maturation that may enable elderly DCs to continuously present antigen. These differences may impact on the efficacy of anti-pathogen and anti-tumour immune responses in the elderly.
