Abstract
SummaryAging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8+ T‐cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8+ T‐cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8+ T‐cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8+ T‐cell responses specific for a model antigen. Reduced CD8+ T‐cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8+ T‐cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.
Highlights
People suffer more often and more severely from infectious and malignant diseases than young individuals
We developed an in vitro assay to assess na€ıve CD8+ T-cell priming directly from unfractionated peripheral blood mononuclear cells (PBMCs)
As circulating human dendritic cell (DC) are rare, DC precursors within the starting PBMC material were mobilized using FLT3 ligand (FLT3L) (Breton et al, 2015), known for its capacity to enhance the induction of T-cell responses (Guermonprez et al, 2013), and matured with a standard cocktail of inflammatory cytokines (TNF, IL-1b, PGE2, and IL-7).we focused on the priming of CD8+ T-cells specific for the melanoma antigen Melan-A/MART-1, restricted by HLA-A*0201 (HLA-A2 from hereon)
Summary
People suffer more often and more severely from infectious and malignant diseases than young individuals. Responses to vaccination are less effective in the elderly. These manifestations are thought to reflect an age-related functional decline in the immune system. An integrated understanding of the aging immune system is essential for the delivery of optimal healthcare to the elderly population. Adaptive immunity mediated by T-cells is critically important in the host response to various pathogens and cells undergoing malignant transformation. Increasing evidence suggests that age-related changes limit the efficacy of cellular immune responses against emerging strains of influenza virus and tumor cells. While recall responses to pathogens encountered earlier in life are largely uncompromised, primary T-cell-mediated immune responses appear to decline with advanced age (Nikolich-Zugich, 2014)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have