Decreased Circulating CD4+CD25highFoxp3+ T Cells During Acute Rejection in Liver Transplant Patients

Background. CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells have been implicated to maintain immunologic tolerance. They have been investigated in acute renal allografts rejection episodes (ARE). This study was performed to examine the frequency of peripheral blood (PB) CD4(+)CD25(high)FoxP3(+) Treg cells among liver transplantation patients with prior benign end-stage liver diseases in relation to ARE. Methods. This prospective analysis of 55 patients who underwent liver transplantation from 2004 to 2009 did not include prisoners either as donors or recipients. PB was obtained from liver transplant patients longitudinally: pretransplantation, posttransplantation within 1 year, and at the time of an episode of ARE to measure by flow cytometry circulating CD4(+)CD25(high)FoxP3(+) T cells. Blood samples were drawn during ARE with concomitant liver biopsies. The rejector group was defined in the 14/55 cases who suffered an ARE; in the other patients with stable liver function were classified as the nonrejector group. We compared the number of circulating CD4(+)CD25(high)FoxP3(+) T cells between the 2 groups. Results. There was no difference in the levels of circulating CD4(+)CD25(high)FoxP3(+) T cells pretransplantation. Interestingly, circulating CD4(+)CD25(high)FoxP3(+) T cells were significantly lower among the rejector compared with the nonrejector (2.23 +/- 0.54% vs 2.99 +/- 0.86%; P <.01). Longitudinal analysis revealed circulating CD4(+)CD25(high)FoxP3(+) T cells of patients in the rejector group to be significantly lower during rejection than during quiescence (2.23 +/- 0.54% vs 3.68 +/- 0.70%; P <.0001). The frequency of circulating CD4(+)CD25(high)FoxP3(+)T cells negatively correlated with a Rejection Activity Index (r = 0.80; P <.01). Conclusion. Monitoring peripheral CD4(+)CD25(high)FoxP3(+)T cell levels may be useful to evaluate the immune state, potentially acting as a sensitive marker for ARE diagnosis among liver transplantation patients. Moreover, they may contribute to the mechanisms of Treg-mediated acceptance of liver transplantations.