Background: To reduce the side effects of long-term immunosuppressive therapy, stable renal transplant patients were routinely converted from cyclosporine to either azathioprine or mycophenolate mofetil. Thereafter, the azathioprine and mycophenolate mofetil dose was reduced to 75% at 4 months and to 50% at 8 months after conversion. We questioned whether the T-cell reactivity before conversion was able to predict which patients could be safely converted and tapered in their immunosuppressive load, while remaining free from acute rejection.
Methods: Before conversion, the T-cell reactivity of peripheral blood mononuclear cells against donor and third-party spleen cells were tested in mixed lymphocyte cultures. We measured the frequency of donor and third-party reactive helper T-lymphocyte (HTLpf) and cytotoxic T-lymphocyte (CTLpf) precursors and their avidity for HLA class I antigens using limiting dilution analysis. Peripheral blood mononuclear cells were also stimulated with tetanus toxoid to test the general immune response.
Results: The tetanus toxoid response, reactivity to donor and third-party cells as measured in mixed lymphocyte cultures and HTLpf, and the avidity of cytotoxic T-lymphocyte precursors were not predictive for the development of acute rejection. However, significant differences were found in donor-specific CTLpf before conversion, between patients with and without acute rejection after conversion in immunosuppression. The donor-specific CTLpf was significantly lower in patients without compared to those with acute rejection (P=0.01). Additionally, when no CTLpf was detectable before conversion, acute rejection did not occur after conversion. Acute rejection was only diagnosed in patients with detectable CTLpf before conversion.
Conclusion: The number of donor-specific cytotoxic T-lymphocytes identifies patients in whom the immunosuppressive load can be safely reduced.