Functional CD25bright+ alloresponsive T cells in fully immunosuppressed renal allograft recipients

Background: Evidence from animal studies indicate a crucial role for CD25(bright+) regulatory T cells in transplantation tolerance. Methos: To assess whether peripheral CD25(bright+) T cells control immune responses in immunosuppressed kidney transplant patients, we analyzed the suppressive capacities of these cells using mixed lymphocytes reactions. Results: Allogeneic stimulation of patients peripheral blood mononuclear cells was associated with IL-2 production and T-cell proliferation. Depletion of CD25(bright+) T cells resulted in a 35% (median) higher IL-2 production and a 38% higher proliferative response against third party cells, showing that functional regulatory CD25(bright+) T cells were present (p = 0.03 and 0.02 respectively). In eight out of 11 patients, we also demonstrated regulation activity against donor-activated T cells (p = 0.03). These data were confirmed in coculture experiments with isolated CD25(-/dim) T cells plus CD25(bright+) T cells. At a 1:2 ratio, the CD25(bright+) T cells suppressed the proliferation of CD25(-/dim) donor- and third party-stimulated responder T cells. Conclusions: CD25(bright+) T cells with immune regulatory activities against anti-donor-responsive T cells are readily detectable in renal allograft recipients during treatment with full dosage immunosuppression. Whether CD25(bright+) T cells indeed play a role in graft acceptance after organ transplantation in patients remains to be elucidated.