High numbers of differentiated CD8+CD28- T cells are associated with a substantially lowered risk for late rejection and graft loss after kidney transplantation
M.G.H. Betjes, A.W. Langerak, M. Klepper, N.H.R. Litjens
Wednesday 13 march 2019
14:04 - 14:06h
at Mauritszaal
Categories: Klinisch, Parallelsessie
Parallel session: Parallelsessie IV - Klinisch I
Background: Recipients of a kidney transplant have a prematurely aged T-cell system. This is reflected in lowered thymic output, reduced telomere length and more highly differentiated T cells. The latter harbor alloreactive cytotoxic memory T cells and are therefore potentially harmful for a kidney transplant. However, recent studies have found an inverse relation between the number of these cells and acute early rejection. In this study, we tested the hypothesis that parameters of an aged T-cell compartment decrease the risk for late rejection after kidney transplantation.
Methods: Recipients of a kidney transplant in the period 2007-2013 were (N=364) were included. T cell telomere length and thymic output were assessed and T cells were characterized prior to transplantation by flow cytometry as naive (CD45RO-CCR7+), central-memory (CD45RO+CCR7+), effector-memory (CD45RO-CCR7-), terminally differentiated CD8+Temra (CD45RO-/CCR7-/CD28-) and CD4+CD28-or CD8+CD28-T cells. Follow-up was until September 2018. The date of the first time of biopsy-proven late rejection (>6 months after transplantation) was used to calculate the rejection-free survival time.
Results: The median follow up time was 79 months. Forty-nine cases of biopsy-proven rejection were recorded of which most were c-aABMR (77.5%), followed by TCMR (10.3%) and mixed type rejections (10.2%). Median time to diagnosis of late rejection was 44 months. Immunological T-cell ageing parameters correlated with calendar age of the recipients. Thymic output and T cell telomere length did not associate with late rejection-free survival. However, the percentage and absolute numbers of CD8+Temra and CD8+CD28-T cells were significantly lower in patients with late rejection. Specifically, in the highest tertile of percentages of CD8+CD28-T cells, the cumulative incidence of late rejection at 5 and 10 years was only 5% and 8% compared to 16% and 20% in the middle to lowest tertile (p=0.002). Multivariate proportional hazard analysis, including clinical relevant parameters and age, showed that percentage and absolute number of CD8+CD28-T cells remained significantly associated with late rejection (p=0.009). In addition, percentage and absolute number of CD8+CD28-T cells (p=0.001) were inversely associated with rejection-related graft loss.
Conclusions: Recipients with high numbers of differentiated CD8+CD28-T cells have a decreased risk for late rejection and rejection-related graft loss after kidney transplantation.
