| dc.description.abstracteng | Abstract
Background. Renal transplantation is an effective method of renal replacement therapy. The success of transplantation depends on the status of immune system of the recipient and its recognition of donor alloantigens. In the induction and maintenance of immune tolerance against alloantigens regulatory T cells (Tregs) of the recipient seem to play an important role. Tregs are differentiated from other T cell populations by the expression of the transcription factor FOXP3, as well as of CD4 and CD25 surface antigens. Various studies claimed peripheral Tregs to influence and prolong the overall survival of kidney allografts. However, the influences of peripheral and tissue regulatory cells are not well understood.
Methods. In this study biopsies of renal allografts of 53 patients were analyzed by immunohistochemistry. In parallel, peripheral mononuclear cells (PBMC) of 29 patients were analyzed by FACS. Tregs were detected by triple-immunofluorescence labelling of cells in tissues and blood for the expression of CD4, CD25, FOXP3. In addition, antibodies against CD3, CD20 and CD14 surface markers were used to differentiate other FOXP3+ cells.
Results. In our study, it was shown that the number of cells with a regulatory phenotype, was reduced in peripheral blood of patients after allogeneic kidney transplantation, in comparison to a healthy control group. Statistically significant correlations between morphological changes of the graft, and the number of peripheral Tregs showing the complete characteristic phenotype (CD4+CD25+FOXP3+), were not found. However, positive correlations between individual markers of Tregs, such as CD4 and FOXP3, and the morphological signs of rejection according to BANFF classification in the allograft were seen. Also, a positive statistically significant correlation between CD3+FOXP3+ cells in the allograft, and morphological signs of rejection according to BANFF classification was found. Furthermore, development of fibrosis and tubular atrophy was associated with increased numbers of CD3+FOXP3+ cells. In addition, other populations of FOXP3-positive lymphocytes such CD20+FOXP3+ and CD14+FOXP3+ were found in the allograft. No statistically significant correlations between these cells and the morphological changes of the allografts were found.
Conclusion. A protective role for rejection reactions of both peripheral as well as of tissue Tregs could not be confirmed in the analyzed transplanted patient group. It could not be excluded that the observed associations between FOXP3+ lymphocytes and morphological signs of rejection reactions were also related to FOXP3 expression in activated effector lymphocytes. Further populations of FOXP3+ cells were seen in the allografts; their role is still unclear. | de |