Impaired production of INF-alpha by dendritic cells of older adults leads to a lower CD8+T cell response against influenza

Wai Ming Liu, Thamar E. R. Nahar, Ronald H. J. Jacobi, Karlijn Gijzen, Josine van Beek, Eelko Hak, Marcel Jonges, Claire J. P. Boog, Bernard A. M. van der Zeijst, Ernst C. Soethout*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Seasonal influenza causes more morbidity and mortality in older adults than in young adults, apparently because of a decline in immune function with increasing age, known as immunosenescence. In this study, we compared the capacity of dendritic cells (DCs) from healthy older adults(>= 65 years) with DCs from healthy young adults (20-40 years) to initiate a T cell response against influenza. DCs from older adults were impaired in the induction of influenza-specific CD8+ T cells as compared to DCs from young adults, which was demonstrated by a decreased proliferation, an impaired production of IFN-gamma and a reduced expression of the degranulation marker CD107a by CD8+ T cells. Importantly, DCs from older adults produced significantly less TNF-alpha, showed a decreased expression of HLA class I and had a lower maturation state after influenza virus infection. Supplementing TNF-alpha increased the expression of HLA class I and of maturation markers and enhanced the induction of the influenza-specific CD8+ T cell response. Together, these findings indicate that the impaired influenza-specific CD8+ T cell response in older adults is associated with a reduced production of TNF-alpha and with a lower DC maturation. We suggest that the production of TNF-alpha is a determining factor in the DC-mediated CD8+ T cell response against influenza. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1659-1666
Number of pages8
JournalVaccine
Volume30
Issue number9
DOIs
Publication statusPublished - 21-Feb-2012

Keywords

  • Influenza
  • Aging
  • Dendritic cells
  • Innate immunity
  • TNF-alpha
  • CD8(+) T-CELLS
  • IMMUNE-RESPONSES
  • AGED MICE
  • LYMPHOCYTE-RESPONSES
  • PERIPHERAL-BLOOD
  • VIRUS-INFECTION
  • A VIRUS
  • VACCINE
  • PROTECTION
  • ANTIGEN

Cite this