International Immunology Advance Access originally published online on January 14, 2008
International Immunology 2008 20(3):375-383; doi:10.1093/intimm/dxm151
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Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype
1 Discipline of Paediatrics, Nepean Clinical School, University of Sydney, Penrith 2751, New South Wales, Australia
2 Centre for Immunology, St Vincents Hospital, Darlinghurst and National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Kensington 2052, New South Wales, Australia
3 Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, Locked Bag 6, Newtown 2042, New South Wales, Australia
Correspondence to: R. Nanan; E-mail: ralphn{at}med.usyd.edu.au
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.
Keywords: CD4+ T cell differentiation, immune regulation
* These authors contributed equally to this study.
Transmitting editor: T. Huenig
Received 19 August 2007, accepted 14 December 2007.
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