The influence of age on T cell generation and TCR diversity

K Naylor, G Li, AN Vallejo, WW Lee, K Koetz… - The Journal of …, 2005 - journals.aai.org
K Naylor, G Li, AN Vallejo, WW Lee, K Koetz, E Bryl, J Witkowski, J Fulbright, CM Weyand
The Journal of Immunology, 2005journals.aai.org
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 …
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× 10 7 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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