Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation.
Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0.04), HTLp-RR (P = 0.04) and CTLp-RR (P = 0.09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0.0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.
van Besouw
N M
NM
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands. vanbesouw@inwl.azr.nl
van der Mast
B J
BJ
de Kuiper
P
P
Smak regoor
P J H
PJ
Vaessen
Lenard M B
LM
Ijzermans
J N M
JN
van Gelder
T
T
Weimar
W
W
D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology