Introduction

A diverse T-cell receptor (TCR) repertoire is central to effective T-cell mediated immune responses to foreign antigens. Patients suffering from end stage renal disease (ESRD) have an impaired T-cell mediated immune system and advanced T-cell ageing is observed in elderly (age >60 years) ESRD patients. Previous studies have shown that age and cytomegalovirus (CMV) latency relates to decreased TCR repertoire diversity, but little is known whether uraemia affects TCR repertoire diversity. The aim of this study is to assess the effects of uraemia on TCR repertoire diversity and relate this to T-cell ageing parameters.

Study population and Methods

Twenty ESRD patients (65—73 years) and 20 healthy individuals (HI; 64—72 years) matched for age, total number of circulating T cells and CMV-serostatus were enrolled. The TCR beta (TCRβ) repertoire was measured by DNA-based multiplex TCRβ gene PCR. Ageing parameters included thymic output (the number of CD31⁺ naive T cells), T cell differentiation status and relative telomere length (RTL).

Results

Eighty percent of the elderly ESRD patients had a narrowed TCRB repertoire (oligoclonal) versus only 40% of the HI (P=0.023). More specifically, within the CMV-seronegative group, 5 out of 9 ESRD patients had an oligoclonal TCRB repertoire versus none of the 7 HI (P=0.034); In the CMV-seropositive group, all 11 ESRD patients had an oligoclonal TCRB repertoire versus 8 of the 13 HI (P=0.041). In addition, ESRD patients with an oligoclonal TCRB repertoire tended to have lower numbers of CD4⁺ CD31⁺ naive (P=0.081) and higher numbers of CD8⁺ EMRA (P=0.081) T cells than those with a more polyclonal repertoire. Moreover, the RTL of CD8⁺ T cells tended to be shorter in patients with an oligoclonal TCRB repertoire than those with a more polyclonal repertoire (P=0.063).

Conclusion

Uraemia decreases TCRB repertoire diversity in elderly ESRD patients and this reduction may relate to lower thymic output, increased numbers of highly differentiated CD8⁺ T cells and shorter telomeres within CD8⁺ T cells. Assessment of TCRB repertoire diversity of elderly ESRD patients on the kidney transplant waiting list may be useful for evaluating the risk of infection and rejection after transplantation.

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