Regulatory T cells in kidney transplant recipients.

Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long-term tolerance. Tolerance to self-antigens is ensured naturally by several mechanisms; one major mechanism depends on the activity of regulatory T lymphocytes (Treg), particularly CD4+CD25+ T cells. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. The direct effects of immunosuppressive drugs on CD4+CD25+ cells are uncertain. In the clinical setting, basiliximab used in the induction phase of immunosuppression effectively reduced the number of acute rejection episodes. We studied the effects of the most widely used immunosuppressive induction regimens including cyclosporine, mycophenolate mofetil, steroids, and anti-CD25 monoclonal antibody (basiliximab) on the capacity to regulate human Treg in vivo. Twenty first cadaveric kidney transplant recipients (14 men, 6 women) were enrolled in the study. Blood samples were collected before kidney transplant and after one month. Blood sampling was done immediately before the administration of immunosuppressive therapy after an overnight fast. None of the transplant recipients presented laboratory or clinical signs of infection or acute rejection. The number and percentage of CD4+CD25+ and Foxp3+ T cells were determined by fluorescence activated cell sorter (FACS) analysis. Our results showed absence of both CD4+CD25+ and CD4+CD25+ Foxp3+ T cells one month after transplant. Peripheral CD4+CD25-Foxp3+ T cells significantly decreased after transplant but did not disappear. These preliminary data suggest that immunosuppressive induction therapy with basiliximab completely suppresses CD4+CD25+ regulatory cells and significantly reduces the total number of Foxp3+ lymphocytes.