title: Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation.
abstract: The uremia-induced inflammatory environment in end-stage renal disease (ESRD) patients is associated with premature T-cell aging resulting in a defective T-cell immunity. As kidney transplantation (KTx) reduces the pro-inflammatory environment, we hypothesized that KTx would rejuvenate the aged T-cell system. As aging parameters, we determined in 70 KTx recipients the differentiation status by immunophenotyping, thymic output by the T-cell receptor excision circle (TREC) content together with CD31(+) naïve T-cell numbers and the relative telomere length (RTL) as a measure for proliferative history at pre-KTx, 3, 6 and 12 months post-KTx. In addition, T-cell function was determined by measuring the proliferative capacity and percentages of cytokine-producing cells. Directly post-KTx, memory T-cell numbers were diminished but restored to pre-KTx values at 12 months, except for CD4(+) EM T cells. The RTL of (memory) CD4(+) and CD8(+) T cells did not change. In contrast, TREC content and CD31(+) naïve T-cell numbers were stable post-KTx although the RTL of naïve CD4(+) and CD8(+) T cells decreased implying homeostatic proliferation of naïve cells, in response to a temporary decrease in memory cells. The T-cell function was not improved post-KTx. Our findings demonstrate that the uremia-associated aged phenotype is stably imprinted in the T-cell system and not reversed by KTx.
authors.affiliation: Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ruud W J
authors.initials: RW
authors.lastname: Meijers
authors.forename: Nicolle H R
authors.initials: NH
authors.lastname: Litjens
authors.forename: Elly A
authors.initials: EA
authors.lastname: de Wit
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure; D016922:Cellular Senescence / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D017582:Renal Replacement Therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D059505:Telomere Homeostasis; D013950:Thymus Gland / Q000276:immunology; D014511:Uremia / Q000276:immunology* / Q000601:surgery / Q000628:therapy
keywords: T cells; T-cell receptor excision circle; aging; end-stage renal disease patients; kidney transplantation; telomeres