Possible defect of T suppressor cell subpopulation in patients with kidney acute rejection

Abstract

CD8(+)CD28(-) forkhead box P3 (Foxp3(+)) T suppressor (Ts) lymphocytes are antigen-specific cells capable of inducing tolerogenic antigen-presenting cells by up-regulation of inhibitory receptors immunoglobulin-like-transcripts -3 and -4 and down-regulation of costimulatory molecules. Our study sought to investigate the relation between the level of peripheral CD8(+)CD28(-)Foxp3(+) Ts cells and kidney allograft outcomes. The project included 44 kidney transplantation patients. During the 6-month period following transplantation an acute rejection episode (ARE) was diagnosed in 11 patients based on biopsy results using the Banff criteria. Peripheral blood samples collected at 1 day before as well as 14 and 30 days after transplantation were tested for CD8(+)CD28(-)Foxp3(+) T cells by means of flow cytometry. Values were considered significant when P < .05. Cytometric analysis did not show significant differences between the groups in pretransplant levels of peripheral CD8(+)CD28(-)Foxp3(+) Ts cells (P > .05); however, the posttransplantation analysis showed a higher mean level of Ts cells in nonrejection (NONARE) versus acute rejection (ARE) patients (P < .0001). This observation suggested that dysfunction of CD8(+)CD28(-)Foxp3(+) Ts cells observed in ARE patients may contribute to these episodes. Interestingly, we observed similar results with respect to peripheral CD4(+)CD25(+)Foxp3(+) T regulatory cells in ARE patients, suggesting impairment of immunoregulatory mechanisms (especially within the inducible Foxp3 system) in this group, leading to acute renal allograft rejection episodes.