An age-related increase in the number of CD8+ T cells carrying receptors for an immunodominant Epstein-Barr virus (EBV) epitope is counteracted by a decreased frequency of their antigen-specific responsiveness.
The aim of this study was to provide a basis for investigating the effects of one very common environmental factor, Epstein-Barr virus (EBV), on age-related changes in the immune system. To this end, the frequency of CD8(+) T cells carrying receptors for an immunodominant EBV lytic epitope was assessed by direct staining with HLA-peptide tetrameric complexes in 19 very old (>87 years) and 12 young (20-40 years) EBV carriers. The frequency of EBV-tetramer-positive cells within the CD8(+) subset was significantly greater in the old compared to the young group (P=0.001). However, the frequency of EBV antigen-specific IFN-gamma producing T cells, as determined by ELISPOT, was significantly lower in the old (P=0.001). Therefore, the absolute number of functional EBV-specific T cells in the elderly and the young was probably similar. These data suggest CD8 clonal expansions in the elderly, resulting in an accumulation of dysfunctional EBV-specific cells which possibly fill the 'immunological space' and could lead to a shrinking of the T cell repertoire for other novel antigens. This may help to explain the increased incidence and case-fatality caused by viruses and intracellular pathogens in the elderly.
Ouyang
Qin
Q
Tuebingen Ageing and Tumour Immunology Group, Center for Medical Research, ZMF, Waldhoernlestr. 22, 72072, Tuebingen, Germany. qin.ouyang@uni-tuebingen.de
Wagner
Wolfgang M
WM
Walter
Steffen
S
Müller
Claudia A
CA
Wikby
Anders
A
Aubert
Geraldine
G
Klatt
Tatjana
T
Stevanovic
Stefan
S
Dodi
Tony
T
Pawelec
Graham
G
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D000939:Epitopes; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007124:Immunoenzyme Techniques; D018655:Lymphocyte Count
D000939:Epitopes; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes