title: Premature aging of circulating T cells in patients with end-stage renal disease.
abstract: Progressive loss of renal function is associated with a dysregulation of circulating T cells that may underlie their impaired T-cell immunity. Here we tested whether end-stage renal disease (ESRD)-related T-cell alterations are compatible with the concept of premature immunological aging. Younger patients (25-45 years old) with ESRD were found to resemble older healthy controls (60-80 years old) as they had a significant loss of naive T cells and a relative increase of memory T cells showing progressive terminal differentiation. A significant decrease in the content of T-cell receptor excision circles and telomere length in patients with ESRD confirmed these phenotypic data. The loss of naive T cells in patients with ESRD was associated with an excessive age-related decrease of recent thymic emigrants, indicating a premature decline in thymic function. Additionally, increased homeostatic proliferation of naive T cells was found in patients with ESRD, similar to that of older healthy individuals, with an increased susceptibility for activation-induced apoptosis. Therefore, both decreased thymic output and increased susceptibility of naive T cells for apoptosis may play a role in the loss of naive T cells in ESRD patients. Thus, our results are compatible with premature aging of the T-cell system of patients with ESRD comparable with that of healthy individuals 20-30 years older.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. m.g.h.betjes@erasmusmc.nl
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Ashley
authors.initials: A
authors.lastname: van der Spek
authors.forename: Elly A
authors.initials: EA
authors.lastname: de Wit
authors.forename: Nicolle H R
authors.initials: NH
authors.lastname: Litjens
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology; D001773:Blood Cells; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology*; D013950:Thymus Gland