Bootcongres

Background 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 (AR patients). For each patient with AR, 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 (p<0.05) as measured by TREC-content and percentages of CD31⁺Ki67^- naïve CD4⁺ and CD8⁺ T cells pre-KTx. The RTL of both CD4⁺ and CD8⁺ T cells did not differ between the two patient groups prior to KTx. Furthermore, the AR patients had a significantly (p<0.05) lower percentage CD4⁺ memory T cells lacking CD28 (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/ml) 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)).