NIV Congres

Background End-stage renal disease (ESRD) patients have a defective T cell mediated immune system which is related to excessive premature ageing of the T cell compartment. This is believed to be caused by the uremia-induced pro-inflammatory conditions. Kidney transplantation (KTx) reduces this pro-inflammatory environment and the aim of this study is to investigate whether KTx is able to reverse premature immunological ageing.

Methods For this purpose, we followed 140 KTx recipients excluding cytomegalovirus (CMV)pos donor/CMVneg recipient combinations as primary CMV infection influences T cell differentiation status. KTx recipients were followed prior to and at 3, 6 and 12 months post KTx and their circulating T cells studied using several T cell ageing parameters. First, thymic output was assessed by determining the T cell receptor excision circle (TREC) content together with % CD31⁺ naïve T cells. Relative telomere length (RTL) was determined as a measure for proliferative history and immunophenotyping was used to establish the differentiation status of circulating T cells.

Results The TREC content, % of CD31⁺ naïve T cells as well as the RTL of CD4⁺ and CD8⁺ T cells remained unaltered within the first year post KTx. The absolute number of CD4⁺ as well CD8⁺ T cells decreased 3 months after KTx mainly due to a decrease in memory T cells and in particular the more differentiated T cells (p<0.001 for both CD4⁺ EM and CD8⁺ EMRA population). At 12 months post transplantation the number of CD8⁺ EMRA T cells reached again pre-KTx values. Remarkably, the number CD4⁺ EM T cell population remained significantly low (p<0.05) within the first year post KTx (i.e. 189.4±15.3 cells/ml pre vs 136.3±13.7 cells/ml at 12 months).

Conclusion The prematurely aged T cell compartment of ESRD patients is not reversed by kidney transplantation. Loss of thymic function and excess of highly differentiated aged T cells seem permanent and therefore remain important determinants of a dysfunctional immune system after transplantation

(This study was financially supported by the Dutch Kidney Foundation (KSPB.10.12)).