Uremia‐associated immunological aging is stably imprinted in the T‐cell system and not reversed by kidney transplantation

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.