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.
|Keywords||aging, end-stage renal disease patients, kidney transplantation, T cells, T-cell receptor excision circle, telomeres|
|Persistent URL||dx.doi.org/10.1111/tri.12416, hdl.handle.net/1765/86075|
Meijers, R.W.J, Litjens, N.H.R, de Wit, E.A, Langerak, A.W, Baan, C.C, & Betjes, M.G.H. (2014). Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation. Transplant International, 27(12), 1272–1284. doi:10.1111/tri.12416