Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype

Abstract

We and others recently described a method for isolating viable forkhead boxp3 (FoxP3+) T regulatory cells (Tregs) by means of the surface phenotype CD4+CD127loCD25+. In this study, we used the new strategy to measure Treg numbers, phenotype and function at different ages. Mean percentages of CD4+ CD127loCD25+ Tregs increased only slightly throughout life, from 6.10% in cord blood to 7.22% in PBMC from adults between 20 and 25 years and 7.50% in PBMC from adults over the age of 60. In all age groups, a higher proportion of Tregs had acquired a CD45RA- memory phenotype compared with CD4+ Foxp3- conventional T cells. This increase was entirely attributable to increased Tregs with an effector memory phenotype, whereas central memory phenotype cells were comparably represented within the Treg and conventional CD4+ T-cell populations. Expression of CD95 also differed between Tregs and conventional CD4+ T cells at all ages. However there was no difference in the suppressive capacity of the different naive and memory Treg subsets. These results suggest that, compared with their conventional CD4+ T-cell counterparts, Tregs undergo preferential differentiation from a naive to an effector memory phenotype, driven by their specificity for self- rather than foreign antigen. However, number and function are remarkably stable throughout life. © The Japanese Society for Immunology. 2008. All rights reserved.