Contrasting CD25hiCD4+T Cells/FOXP3 Patterns in Chronic Rejection and Operational Drug-Free Tolerance

Background. Although immunosuppression withdrawal in kidney recipients usually leads to rejection, in some patients it does not, leading to a state of clinical operational tolerance. Methods. We compared these highly contrasted situations by analyzing blood cell phenotype and transcriptional patterns in drug-free spontaneously tolerant kidney recipients, recipients with chronic rejection, recipients with stable graft function under standard or minimal immunosuppression and healthy individuals Results. The blood cell phenotype of clinically tolerant patients did not differ from that of healthy individuals. In contrast, recipients with chronic rejection had significantly less CD25hiCD4+T cells and lower levels of FOXP3 transcripts compared with clinically tolerant recipients. Patients with chronic rejection also displayed CD25−CD4+T cells expressing NKG2D+CD94+ and CD57+CD27−CD28− cytotoxic-associated markers (P<0.05). Conclusion. These data show that whereas clinically tolerant recipients displayed normal levels of CD25hiCD4+T cells and FOXP3 transcripts, chronic rejection is associated with a decrease in CD25hiCD4+T cells and FOXP3 transcripts, suggesting that clinically “operational tolerance” may be due to a maintained phenomenon of natural tolerance that is lacking in patients with chronic rejection.