Background.: In the search for mechanisms that can induce and maintain transplant tolerance, donor-specific CD4CD25FoxP3 regulatory T cells have been frequently mentioned. However, it remains to be demonstrated, whether these cells are generated after clinical transplantation. Methods.: We prospectively analyzed the phenotype and function of peripheral regulatory CD4CD25 T cells of 79 patients before, 3, 6, and 12 months after kidney transplantation. The immune regulatory capacities of CD4CD25 T cells were assessed by their depletion from peripheral blood mononuclear cells and in co-culture with CD25 responder T-cells in the mixed lymphocyte reactions. Results.: In the first year after transplantation, the number and proportion of CD4CD25 T cells significantly decreased (P<0.05 and P<0.001, respectively). In the mixed lymphocyte reactions, we observed donor-specific hyporesponsiveness in the presence of significantly increased proliferation to third and fourth Party-Ag, (P<0.001 and P<0.05, respectively). Furthermore, functional analysis of CD25 cells showed that the effect of depletion of these cells from peripheral blood mononuclear cells, and their suppressive capacities in co-culture with donor-Ag stimulated CD25 responder T-cells (1:10 ratio) significantly improved (P<0.01 and P<0.001, respectively). Moreover, the difference between the stimulation with donor-Ag and third Party-Ag became apparent at 6 months after transplantation. Conclusions.: These findings demonstrate that donor-specific CD4CD25 regulatory T-cell function is generated in fully immunosuppressed renal recipients in the first year after transplantation.

CD25+ T lymphocyte, CD4+ CD25+ T lymphocyte, Clinical kidney transplantation, Donor-specific regulatory T cells, FOXP3 protein, Immunosuppressive drugs, adult, aged, article, cell specificity, chronic kidney failure, donor, drug megadose, female, forkhead transcription factor, human, immunology, immunoregulation, immunosuppressive agent, interleukin 2 receptor alpha, kidney graft rejection, kidney transplantation, leukocyte antigen, lymphocyte count, lymphocyte depletion, lymphocyte function, major clinical study, male, meprednisone, methylprednisolone sodium succinate, middle aged, mixed lymphocyte culture, mixed lymphocyte reaction, mycophenolic acid 2 morpholinoethyl ester, peripheral blood mononuclear cell, peritoneal dialysis, phenotype, priority journal, prospective study, rapamycin, regulatory T lymphocyte, renal replacement therapy, statistics, tacrolimus, unspecified side effect,
Erasmus MC: University Medical Center Rotterdam

Hendrikx, T.K, van Gurp, E, Sewgobind, V.D.K.D, Mol, W.M, Schoordijk, W, Klepper, M, … Baan, C.C. (2009). Generation of donor-specific regulatory t-cell function in kidney transplant patients. Transplantation, 87(3), 376–383. doi:10.1097/TP.0b013e3181901b69