Functional CD25bright+ alloresponsive T cells in fully immunosuppressed renal allograft recipients
Article first published online: 11 OCT 2006
Volume 21, Issue 1, pages 63–71, January/February 2007
How to Cite
Baan, C. C., Velthuis, J. H.L., Van Gurp, E. A.F.J., Mol, W. M., Klepper, M., Ijzermans, J. N.M. and Weimar, W. (2007), Functional CD25bright+ alloresponsive T cells in fully immunosuppressed renal allograft recipients. Clinical Transplantation, 21: 63–71. doi: 10.1111/j.1399-0012.2006.00584.x
- Issue published online: 2 JAN 2007
- Article first published online: 11 OCT 2006
- Accepted for publication 16 August 2006
- CD4+ CD25bright+ regulatory T cells;
- kidney transplantation;
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.