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

Autor: Wai Ming Liu, Bernard A. M. van der Zeijst, Claire J. P. Boog, Ronald Jacobi, Karlijn Gijzen, Eelko Hak, Thamar E. R. Nahar, Marcel Jonges, Josine van Beek, Ernst C. Soethout
Přispěvatelé: Microbes in Health and Disease (MHD), Methods in Medicines evaluation & Outcomes research (M2O)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Aging
Genes
MHC Class I
VACCINE
CD8-Positive T-Lymphocytes
medicine.disease_cause
Dendritic cells
0302 clinical medicine
AGED MICE
Influenza A virus
Cytotoxic T cell
PROTECTION
Innate immunity
Immunity
Cellular
0303 health sciences
biology
IMMUNE-RESPONSES
Age Factors
Immunosenescence
Recombinant Proteins
3. Good health
Infectious Diseases
Molecular Medicine
Female
TNF-alpha
Adult
LYMPHOCYTE-RESPONSES
ANTIGEN
Human leukocyte antigen
VIRUS-INFECTION
CD8(+) T-CELLS
PERIPHERAL-BLOOD
Interferon-gamma
Young Adult
03 medical and health sciences
Immune system
Antigen
A VIRUS
Influenza
Human
MHC class I
medicine
Humans
Aged
030304 developmental biology
General Veterinary
General Immunology and Microbiology
Tumor Necrosis Factor-alpha
Influenza A Virus
H3N2 Subtype
Public Health
Environmental and Occupational Health
Influenza
Immunology
biology.protein
CD8
030215 immunology
Zdroj: Vaccine
Vaccine, 30(9), 1659-1666. ELSEVIER SCI LTD
Vaccine, 30(9), 1659-1666
Vaccine; Vol 30
ISSN: 0264-410X
1659-1666
DOI: 10.1016/j.vaccine.2011.12.105
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: