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

Ouyang, Qing; Wagner, Wolfgang; Walter, Steffen; Müller, Claudia; Wikby, Anders; Aubert, Geraldine; Klatt, Tatjana; Stevanović, Stefan; Dodi, Tony; Pawelec, Graham

doi:10.1016/s0047-6374(03)00026-5

Cited by 102 publications

(58 citation statements)

References 47 publications

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“…Although some T-cell functions are decreased with age, others are maintained or increased, the latter exemplified by the CMV-specific memory T-cell population, which can occupy a quarter or more of the whole T-cell repertoire (81,82). These cells display the CD8 + CD28 -CCR7 -CD45RA + KLRG + CD57 + phenotype of late-differentiated T cells (Table 1; Ref.…”

Section: T Cells At the Population Levelmentioning

confidence: 99%

“…One putative intervention to restore a balanced T-cell subset distribution would be to deplete excess and possibly dysfunctional CMV-specific T cells but at the same time to maintain strict control of this potentially dangerous viral infection. Because CMV infection is asymptomatic in healthy individuals, it is difficult to know the time of first infection except in the case of CMV-seronegative patients receiving an organ from a in the very old are associated with CMV, has provided additional support for the hypothesis that CMV contributes markedly to the development of an IRP and thus constitutes a good biomarker of immunosenescence in the elderly (81,93).…”

Section: T Cells At the Population Levelmentioning

confidence: 99%

“…Inflamm-aging is the end result of such a process characterized by activation of macrophages and expansion of specific clones (megaclones) of T lymphocytes directed toward antigens of common viruses such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV) (FIGURE 1; Refs. 31,49,81,85,116). All these phenomena have a strong genetic component, as shown by studies in old people and centenarians, which collectively established that the frequency of several variants (polymorphisms) of important genes involved in immune responses and inflammation are present at a different frequency in long-lived people compared with young subjects (FIGURE 1; Refs.…”

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confidence: 93%

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Aging of the Immune System as a Prognostic Factor for Human Longevity

et al. 2008

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Section: T Cells At the Population Levelmentioning

confidence: 99%

Section: T Cells At the Population Levelmentioning

confidence: 99%

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confidence: 93%

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Aging of the Immune System as a Prognostic Factor for Human Longevity

et al. 2008

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“…Overall, this process has the potential to generate an enormous diversity (Ͼ10 15 ) (1) of TCR␣␤s in the thymus, although only a small proportion of these survives thymic selection. The human body accommodates ϳ10 12 T cells in the periphery at any given time, consisting of ϳ10 7 different TCR␣␤s (2). The two herpes viruses, CMV and EBV, infect the majority of the population.…”

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confidence: 99%

TCR β-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV

Venturi

Chin

Asher

et al. 2008

The Journal of Immunology

105

133

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The CD8؉ TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCR␤ chains between individuals is strongly associated with TCR␤ production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCR␤ sequences. In this study, we analyzed a total of 2836 TCR␤ sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCR␤ sequences in the CD8 ؉ T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCR␤ amino acid sequences were found to have two features that indicate efficient TCR␤ production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCR␤ production frequency was predictive of the extent to which both TCR␤ nucleotide and amino acid sequences were shared in vivo. These results suggest that TCR␤ production frequency plays an important role in the interindividual sharing of TCR␤ sequences within CD8 ؉ T cell responses specific for CMV and EBV.

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“…In älteren Individuen scheint die T-Zell-Antwort grundlegend gestört zu sein [105][106][107]. Klonale CD8-positive T-Zellen mit einem reifen Gedächtniszellphänotyp und reduzierter Funktionalität akkumulieren aufgrund einer altersassoziierten verringerten Kapazität, neue naive T-Zellen zu generieren [108,109]. Folglich akkumulieren oligoklonale T-Zell-Populationen mit geringerer Epitopspezifität …”

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