The Influence of Age on T Cell Generation and TCR Diversity

  • Naylor K
  • Li G
  • Vallejo A
  • et al.
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Abstract

The ability to mount protective immune responses depends on the diversity of T cells. T cell diversity may be compromised by the declining thymic output of new T cells. The aging process imposes a threat to diversity, because thymic function deteriorates. In this study we have examined the relationship between thymic production, homeostatic T cell proliferation and TCR β-chain diversity in young (∼25 years), middle-aged (∼60 years), and elderly adults (∼75 years). TCR excision circles (TREC) as a marker of thymic output exponentially decreased by >95% between 25 and 60 years of age. The frequency of Ki67+ cycling CD4 T cells remained steady, and surprisingly, the diversity of the naive CD4 T cell repertoire was maintained at ∼2 × 107 different TCR β-chains. After the age of 70 years, TRECs only slightly declined, but homeostatic proliferation doubled. The diversity of the T cell pool drastically contracted to 200,000 TCR β-chains. Also, the phenotypic distinction between naive and memory CD4 T cells became fuzzy. The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment.

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APA

Naylor, K., Li, G., Vallejo, A. N., Lee, W.-W., Koetz, K., Bryl, E., … Goronzy, J. J. (2005). The Influence of Age on T Cell Generation and TCR Diversity. The Journal of Immunology, 174(11), 7446–7452. https://doi.org/10.4049/jimmunol.174.11.7446

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