Functional analysis of CD4+ CD25bright T cells in kidney transplant patients: improving suppression of donor-directed responses after transplantation.
BACKGROUND
The role of CD4(+) CD25(bright) regulatory T cells (Treg) in controlling alloreactivity is established, but little is known whether antigen-specific Treg are induced in fully immunosuppressed kidney transplant patients.


METHODS
The frequency and function of CD25(bright) T cells of nine stable kidney transplant patients before and 0.5-2 yr after transplantation were measured. Patients received triple therapy consisting of cyclosporine, mycophenolate mofetil and prednisone. To investigate the influence of transplantation and immunosuppression on Treg function, we compared their suppressive capacities pre- and post-transplantation using mixed lymphocyte reactions and kept the CD25(-/dim) effector T-cell (Teff) population constant.


RESULTS
After transplantation, the percentage of CD4(+) CD25(bright) T cells significantly decreased from 8.5% pre-transplant to 6.9% post-transplant (median, p = 0.05). However, the lower percentage of post-transplant CD4(+) CD25(bright) T cells was not associated with reduced, but rather improved suppressor function of these cells. The proliferative response of pre-transplant Teff to donor-antigens was more profoundly suppressed by post-transplant Treg than by pre-transplant Treg (pre-transplant 18% vs. post-transplant 55% median, p = 0.03) and was comparable against third party antigens at a CD25(bright):CD25(-/dim) ratio of 1:20.


CONCLUSIONS
In immunosuppressed kidney transplant patients, the donor-directed suppressive capacity of CD4(+) CD25(bright) regulatory T cells improved, which may contribute to the development of donor-specific hyporesponsiveness against the graft.
Sewgobind
Varsha D K D
VD
Departments of Internal Medicine and Surgery Erasmus MC, University medical Center, Rotterdam, The Netherlands. v.sewgobind@erasmusmc.nl
van der Laan
Luc J W
LJ
Klepper
Mariska
M
Ijzermans
Jan N M
JN
Tilanus
Huug W
HW
Weimar
Willem
W
Baan
Carla C
CC
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D015331:Cohort Studies; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*