Functional CD25(bright+) 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.


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.
Baan
Carla C
CC
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. c.c.baan@erasmusmc.nl
Velthuis
Jurjen H L
JH
van Gurp
Evelien A F J
EA
Mol
Wendy M
WM
Klepper
Mariska
M
Ijzermans
Jan N M
JN
Weimar
Willem
W
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
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit