CHARACTERISTICS OF GRAFT-INFILTRATING LYMPHOCYTES AFTER HUMAN HEART-TRANSPLANTATION - HLA MISMATCHES AND THE CELLULAR IMMUNE-RESPONSE WITHIN THE TRANSPLANTED HEART

The influence of HLA mismatches between donor and recipient on the phe notypes, function, and specificity of T-lymphocyte cultures derived fr om endomyocardial biopsies was studied in 118 heart transplant recipie nts. In case of HLA-DR mismatches, the majority of the EMB-derived cul tures were dominated by CD4(+) T cells while, in patients with HLA-A a nd -B mismatches but without DR mismatches, CD8(+) T cells comprised t he predominant T-cell subset. Cytotoxicity against donor antigens was observed in 75% of the cultures. A significantly (P < 0.005) lower pro portion of the cultures showed cytotoxicity against HLA-A antigens (36 %) when compared with HLA-B (53%) or HLA-DR (49%). An HLA-A2 mismatch elicited a cytotoxic response that was comparable to that found agains t HLA-B and -DR antigens: 62% of the cultures from HLA-A2 mismatched d onor-recipient combinations was reactive against A2. A higher number o f A, B, or DR mismatches resulted in a higher number of cytotoxic cult ures directed against these antigens. A higher number of HLA-B and -DR mismatches was associated with a lower freedom from rejection. Our da ta indicate that, despite the use of adequate immunosuppressive therap y, the degree of HLA matching plays a crucial role in the immune respo nse against a transplanted heart, resulting in a significant effect on freedom from rejection.