Induction of cytotoxic T lymphocytes with destructive potential after cardiac valve homograft implantation

Background and aim of the study: Clinical and experimental studies have sho wn that a specific immunological response may play a role in the degenerati on of human cardiac valve homografts. In heart and corneal transplantation, cytotoxic T lymphocytes (CTL) with high avidity for donor antigens are pre sumed to be the major effector cells causing graft destruction. We studied the kinetics of these donor-specific CTL precursors (CTLp) and their high-a vidity fraction in peripheral blood of patients receiving a cryopreserved v alve homograft. Methods: Limiting dilution analysis (LDA) was used to enumerate donor-speci fic CTLp in peripheral blood samples of 15 patients, obtained up to 12 mont hs after valve implantation. Donor-specificity was proven by using donor-HL A mismatched third-party stimulation cells as controls. CD8 monoclonal anti bodies were used to distinguish high- and low-avidity CTLp. Results: A significant increase in total donor-specific CTLp among the peri pheral blood mononuclear cell population occurred in 14/15 patients (93%) a t 3-6 months (p = 0.045) after implantation and remained so for up to 12 mo nths (p = 0.015). In addition, a significant increase was seen in the fract ion of circulating CTLp with high avidity for donor antigens (p < 0.026) wi thin the first 3 months after implantation. Conclusion: Implantation of cryopreserved valve homografts increases the nu mber of donor-specific CTLp and their high-avidity fraction, in the periphe ral blood. These cells have the capacity to destroy organ and tissue grafts .