期刊
KIDNEY INTERNATIONAL
卷 84, 期 6, 页码 1226-1236出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ki.2013.236
关键词
effector/memory T cells; IFN-gamma Elispot; immune-monitoring; kidney transplantation
资金
- Pfizer
- European commission [512090]
- Spanish Red de Investigacion Renal (REDinREN) [ISCIII 06/0016]
- [FIS EC07/90382]
- [PI07/0688]
- [PI10/01786]
Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-gamma Elispot has been shown to distinguish patients at risk for immune-mediated graft dysfunction, suggesting a potential tool for immunosuppression individualization. In this nonrandomized study, we prospectively assessed donor and nondonor T-cell alloreactivity in 60 highly alloreactive patients receiving calcineurin inhibitor-based immunosuppression and in non-T-cell alloreactive transplant recipients treated with a calcineurin inhibitor-free regimen. The impact was evaluated using 1-year allograft outcome. We found a strong association between ongoing antidonor T-cell alloreactivity and histological lesions of acute T cell-mediated rejection in 6-month protocol biopsies, distinguishing those patients with better 1-year graft function, regardless of immunosuppression regimen. Interestingly, evidence for enhanced immune regulation, driven by circulating Foxp3-demethylated regulatory T cells, was only observed among patients achieving antidonor T-cell hyporesponsiveness. Thus, prospective evaluation of donor-specific T-cell sensitization may add crucial information on the alloimmune state of transplanted patients to be used in daily clinical practice.
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