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Keywords:

  • CD4+ CD25bright+ regulatory T cells;
  • kidney transplantation;
  • patients

Abstract:  Background:  Evidence from animal studies indicate a crucial role for CD25bright+ regulatory T cells in transplantation tolerance.

Methods:  To assess whether peripheral CD25bright+ 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 CD25bright+ 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 CD25bright+ 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 CD25bright+ T cells. At a 1:2 ratio, the CD25bright+ T cells suppressed the proliferation of CD25−/dim donor- and third party-stimulated responder T cells.

Conclusions:  CD25bright+ 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 CD25bright+ T cells indeed play a role in graft acceptance after organ transplantation in patients remains to be elucidated.