Thymic Output Prior to Kidney Transplantation Is Associated With the Risk for Acute Rejection.

Abstract

Study's purpose The uremia-induced inflammatory environment in end-stage renal disease (ESRD) patients is associated with premature T-cell ageing, which results in defective T-cell-mediated immunity. Since T cells play a major role in acute rejection (AR), we hypothesized that an aged T-cell compartment prior to kidney transplantation (KTx) is associated with a lower risk for AR post-KTx. Methods For this purpose, we analyzed pre-KTx samples of 20 kidney transplant recipients with a biopsy-proven AR within three months post-KTx. For each AR patient, two non-rejectors (NR) were included, matched for age, number of HLA-mismatches and cytomegalovirus serostatus. Thymic output was assessed by determining the T-cell receptor excision circle (TREC) content and percentages of CD31+(Ki67-) naïve T cells as recent thymic emigrants (RTEs). The 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 Interestingly, the AR patients had a significantly higher thymic output as measured by TREC-content (p<0.05) and percentages of CD31+Ki67- naïve CD4+ and CD8+ T cells (p<0.01) pre-KTx. The RTL of both CD4+ and CD8+ T cells did not differ between the two patient groups pre-KTx. Furthermore, the AR patients had a significantly (p<0.05) lower percentage CD4+CD28null memory T cells (2.75±0.95% vs. 5.11±1.02%). For the CD8+ T-cells, AR patients had a significantly (p<0.05) higher number of central memory cells (32.3±5.00 vs. 20.62±2.77 cells/ul) compared to the matched NR. Conclusion An aged T-cell phenotype together with a lower thymic output prior to KTx is associated with a lower risk for AR. (This study was financially supported by the Dutch Kidney Foundation (KSPB.10.12)).