The role of Foxp3+ regulatory T cells in kidney transplantation.

Our project aimed to investigate the relation between the level of pretransplantation and posttransplantation peripheral CD4(+)CD25(+)Foxp3(+) T-regulatory lymphocytes (Tregs) and the development of acute rejection (AR) episodes in 44 patients after kidney transplantation. During the 6-month period following transplantation, AR was diagnosed in 11 patients. Peripheral blood samples were collected 1 day before and 10 days after transplantation and tested for concentrations of CD4(+)CD25(+)Foxp3(+) cells by means of flow cytometry. The pretransplantation analysis showed significantly lower mean levels of peripheral Tregs in AR patients versus control group (P < .05). A lower level of Tregs was also observed in nonrejection (NONAR) patients versus control group (P < .05); however, it was still higher than in the AR group (P < .05). The 10-day posttransplantation analysis showed a similar pattern; however, a significant increase in the concentration of peripheral Tregs in NONAR patients was observed (P < .05), whereas no change was recorded in AR patients (P > .05). We found lower pretransplantation levels of peripheral Tregs in both AR and NONAR groups, versus control group. The deficiency of peripheral Tregs in patients with end-stage renal failure might be due to the long-term inflammatory processes adversely affecting the peripheral regulatory mechanisms. However, significantly lower levels of Tregs observed in AR patients might also be related to genetic predispositions. Our observation suggests that the size and possibly the functionality of Tregs in the AR group was not sufficient to successfully control the immune response after kidney transplantation, leading to acute rejection episodes.