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  • Title: Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.
    Author: van der Mast BJ, van Besouw NM, de Kuiper P, Vaessen LM, Gregoor PJ, IJzermans JN, van Gelder T, Claas FH, Weimar W.
    Journal: Transplantation; 2001 Sep 15; 72(5):873-80. PubMed ID: 11571453.
    Abstract:
    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</=20; 13/13 vs. 12/25, P=0.001) and an undetectable helper T lymphocyte precursor frequency (<10/106 peripheral blood mononuclear cells; 7/7 vs. 17/30, P=0.04) before transplantation did not experience acute rejection. The donor-specific cytotoxic T lymphocyte precursor frequency (n=34; median 53/106 vs. 28/106, P=0.58) and tetanus toxoid-reactivity (n=38; median stimulation index: 53 vs.16, P=0.56) measured before transplantation did not correlate with acute rejection. No correlation between third-party reactivity and acute rejection was observed. 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.
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