Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.

Background: A reliable immunological assay for quantification of donor-specific alloreactivity to identify patients at risk for future allograft rejection would be a helpful tool in organ transplantation. Therefore, we questioned whether the T cell reactivity in patients measured before transplantation was predictive for the occurrence of acute rejection during the first year after kidney transplantation.

Methods: The pretransplant T cell reactivity of peripheral blood mononuclear cells to donor and third-party antigens was tested in mixed lymphocyte cultures, and to tetanus toxoid. In addition, we measured the frequency of donor and third-party reactive helper T lymphocyte precursor and cytotoxic T lymphocyte precursors using limiting dilution analysis.

Results: Patients who experienced acute rejection had significantly higher donor-specific mixed lymphocyte cultures responses (n=38; median stimulation index): 113 vs. 15, P=0.005) and helper T lymphocyte precursor frequency (n=37; median 194/106 vs. 62/106, P=0.009) measured before transplantation compared to patients without acute rejection. All patients with a low mixed lymphocyte culture response (stimulation index
Conclusions: From these results we conclude that despite the current HLA matching criteria, undetectable helper T lymphocyte precursor frequency and low mixed lymphocyte culture responses against donor antigens measured before transplantation are predictive for a rejection-free first posttransplant year. These in vitro assays can be used to identify patients who require less immunosuppression after transplantation.