TY - JOUR
T1 - The influence of age on T cell generation and TCR diversity
AU - Naylor, Keith
AU - Li, Guangjin
AU - Vallelo, Abbe N.
AU - Lee, Won Woo
AU - Koetz, Kerstin
AU - Bryl, Ewa
AU - Witkowski, Jacek
AU - Fulbright, James
AU - Weyand, Cornelia M.
AU - Goronzy, Jörg J.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=21044451726&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.174.11.7446
DO - 10.4049/jimmunol.174.11.7446
M3 - Article
C2 - 15905594
AN - SCOPUS:21044451726
SN - 0022-1767
VL - 174
SP - 7446
EP - 7452
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -