Abstract
BackgroundEnd-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR).Methods222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters.ResultsOf the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001).ConclusionImmunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.
Highlights
We hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR)
A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028)
Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR
Summary
Loss of renal function leads to retention of uremic molecules and cytokines, which creates oxidative stress and inflammation. [1] The resulting pro-inflammatory uremic environment underlies the dysfunctional T-cell immunity of end-stage renal disease (ESRD) patients. [2] The major changes in the peripheral T-cell composition are T-lymphopenia, increased T-cell differentiation and loss of telomere length, the latter indicating a history of enhanced T-cell replication. [3]The T-lymphopenia is largely due to a loss of naive (antigen-inexperienced) T cells, which show signs of increased activation and are more prone to apoptosis. [3] This loss of circulating naive T cells runs in parallel with a decrease in newly formed naive T cells, known as recent thymic emigrants (RTEs, indicating a premature involution of the thymus). The uremia-associated changes in the composition of the peripheral T-cell compartment resemble the physiological changes in the ageing immune system of elderly healthy individuals, [8,9,10] which leads to the concept of ESRD-related premature immunological ageing This was confirmed when a combined analysis of the thymic output, differentiation status and the telomere length of T cells in ESRD patients was performed and the results were compared to healthy individuals over a wide age range. We hypothesized that the degree of premature T-cell ageing, based on the absolute number of differentiated T cells, thymic output and telomere length, prior to kidney transplantation (KT) is associated with the risk for early acute allograft rejection (EAR) in kidney transplant recipients. We hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
