After discontinuation of calcineurin inhibitors, tapering of mycophenolate mofetil further impairs donor-directed cytotoxicity
Article first published online: 2 SEP 2007
© 2007 Blackwell Munksgaard
Volume 22, Issue 2, pages 129–135, March/April 2008
How to Cite
Van Besouw, N. M., Van De Wetering, J., Van Der Mast, B. J., De Kuiper, R., Baan, C. C. and Weimar, W. (2008), After discontinuation of calcineurin inhibitors, tapering of mycophenolate mofetil further impairs donor-directed cytotoxicity. Clinical Transplantation, 22: 129–135. doi: 10.1111/j.1399-0012.2007.00754.x
- Issue published online: 2 SEP 2007
- Article first published online: 2 SEP 2007
- Accepted for publication 11 July 2007
- immune monitoring;
- tapering immunosuppression;
- T cells;
Abstract: Background: Recently, we described a significant decrease in donor-specific cytotoxic T-lymphocyte precursor frequency (CTLpf) after discontinuation of calcineurin inhibitors (CNI), while the proliferative capacity in mixed lymphocyte culture (MLC), and the number of interferon-γ (IFN-γ) producing cells (pc) in Elispot remained unchanged.
Methods: We tested T-cell reactivity in CNI free patients with stable renal graft function, on mycophenolate mofetil (MMF) or azathioprine (AZA) plus prednisone, who were tapered to 50% of their MMF or AZA dose.
Results: Furthermore, tapering of the MMF or AZA dose resulted in a decrease of donor-reactive CTLpf in all patients with detectable CTLpf. Detectable numbers decreased from a median of 32 to 8 CTLp/106 peripheral blood mononuclear cell (PBMC). No effect on third-party reactive CTLpf was found, while the T-cell reactivity to donor and third-party cells as tested in MLC and in IFN-γ Elispot was not affected either by tapering of immunosuppression. Third-party reactivity was significantly higher than donor-specific reactivity in all tests. A control group showed no changes in any of the in vitro assays.
Conclusion: Both withdrawal of CNI and tapering of MMF or AZA dose decreases the donor-specific CTLpf. Our data suggest that reduction of immunosuppression results in a specific decrease of donor-directed cytotoxic capacity of immunocompetent cells, while their proliferation and cytokine production capacity remained unchanged. Immunosuppression hinders development of cytotoxic non-responsiveness.