STIMULATION OF IMMUNE-COMPETENT CELLS IN-VITRO BY HUMAN CARDIAC VALVE-DERIVED ENDOTHELIAL-CELLS

Both fresh and cryopreserved human cardiac valve allografts are transp lanted without matching donor and recipient for blood group or human l eukocyte antigens (HLA) and without the usual immunosuppressive therap y that follows organ transplantation. Calcification occurs in almost a ll transplanted valves, and in children acute valve failure is frequen tly seen. We hypothesized that failure of the human valve allografts c ould have an immunologic basis. This hypothesis was tested in a functi onal way by performing lymphocyte stimulation assays using fresh and c ryopreserved valve pieces and endothelial cells derived from valve lea flets as stimulator. Human peripheral blood lymphocytes, both matched and mismatched for HLA antigens, were used as responder cells. The res ults were expressed as the stimulation index. Fresh valve pieces induc ed a significantly higher stimulation index (median, 9; range, 4 to 11 7) compared with the cryopreserved pieces (median, 2; range, 0 to 9; p = 0.002 by Wilcoxon test). The stimulation index was significantly re duced when lymphocytes matched for HLA-DR with the valve pieces were u sed (median, 1; range, 0 to 5) as compared with the HLA-DR-mismatched combination (median, 4; range, 2 to 117; p = 0.006, Wilcoxon test). Va lve leaflet-derived endothelial cells were able to induce a median sti mulation index of 8 (range, 3 to 15) when incubated with lymphocytes m ismatched for HLA-A, -B, and -DR. In conclusion, stimulation of immune -competent tells in vitro is induced by both fresh and cryopreserved h uman valve pieces and by endothelial cells derived from fresh valve le aflets. The immune response can be reduced by using cryopreserved valv es or by matching valve donor and responder lymphocytes for HLA-DR. Vi able endothelial cells, present on fresh but not on cryopreserved valv es, could play a major role in the high antigenicity of fresh valves.