Impaired production of TNF-α by dendritic cells of older adults leads to a lower CD8+ T cell response against influenza.
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-γ and a reduced expression of the degranulation marker CD107a by CD8+ T cells. Importantly, DCs from older adults produced significantly less TNF-α, showed a decreased expression of HLA class I and had a lower maturation state after influenza virus infection. Supplementing TNF-α 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-α and with a lower DC maturation. We suggest that the production of TNF-α is a determining factor in the DC-mediated CD8+ T cell response against influenza.
Department of Vaccinology, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Wai Ming
WM
Liu
Thamar E R
TE
Nahar
Ronald H J
RH
Jacobi
Karlijn
K
Gijzen
Josine
J
van Beek
Eelko
E
Hak
Marcel
M
Jonges
Claire J P
CJ
Boog
Bernard A M
BA
van der Zeijst
Ernst C
EC
Soethout
D000328:Adult; D000367:Age Factors; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005805:Genes, MHC Class I; D006801:Humans; D007111:Immunity, Cellular; D053122:Influenza A Virus, H3N2 Subtype; D007251:Influenza, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*; D055815:Young Adult
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma