Aging Impairs the Ability of Conventional Dendritic Cells to Cross-Prime CD8+ T Cells upon Stimulation with a TLR7 Ligand

PLoS One. 2015 Oct 16;10(10):e0140672. doi: 10.1371/journal.pone.0140672. eCollection 2015.

Abstract

The aging process is accompanied by altered immune system functioning and an increased risk of infection. Dendritic cells (DCs) are antigen-presenting cells that play a key role in both adaptive and innate immunity, but how aging affects DCs and their influence on immunity has not been thoroughly established. Here we examined the function of conventional DCs (cDCs) in old mice after TLR7 stimulation, focusing on their ability to cross-prime CD8+ T cells. Using polyU, a synthetic ssRNA analog, as TLR7 ligand and OVA as an antigen (Ag) model, we found that cDCs from old mice have a poor ability to stimulate a CD8+ T cell-mediated cytotoxic response. cDCs from old mice exhibit alterations in Ag-processing machinery and TLR7 activation. Remarkably, CD8α+ cDCs from old mice have an impaired ability to activate naïve CD8+ T cells and, moreover, a lower capacity to mature and to process exogenous Ag. Taken together, our results suggest that immunosenescence impacts cDC function, affecting the activation of naïve CD8+ T cells and the generation of effector cytotoxic T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Antigen Presentation*
  • Antigens / immunology
  • Antigens / pharmacology
  • CD8-Positive T-Lymphocytes / enzymology*
  • Cross-Priming / drug effects
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Immunity, Cellular*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Poly U / immunology
  • Poly U / pharmacology
  • Toll-Like Receptor 7 / immunology*

Substances

  • Antigens
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Poly U

Grants and funding

This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica (PICT 2012-0591), Fundación Antorchas, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET, PIP 11220120100420), Universidad Nacional de Córdoba and Fundación Florencio Fiorini. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.