title: Functional CD25(bright+) alloresponsive T cells in fully immunosuppressed renal allograft recipients.
abstract: BACKGROUND
  Evidence from animal studies indicate a crucial role for CD25(bright+) regulatory T cells in transplantation tolerance.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. c.c.baan@erasmusmc.nl
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Jurjen H L
authors.initials: JH
authors.lastname: Velthuis
authors.forename: Evelien A F J
authors.initials: EA
authors.lastname: van Gurp
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Mol
authors.forename: Mariska
authors.initials: M
authors.lastname: Klepper
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit