Beneficial and detrimental human leucocyte antigen (HLA)-DR mismatches arenot reflected by a differential effect of immunosuppressive drugs on the in vitro alloimmune response

The introduction of molecular tissue typing techniques has led to an enormo us increase in the number of human leucocyte antigen (HLA) alleles. This in creasing polymorphism of the HLA antigens makes the selection of a well-mat ched unrelated donor a difficult task. Recent data suggest that some HLA mi smatches are more immunogenic than others. This has led to the introduction of terms like beneficial or acceptable versus detrimental or taboo mismatc hes. The study considered whether the differential immunogenicity as reflec ted by graft survival studies can be detected in vitro as well. Mixed lymph ocyte reaction (MLR) and primed lymphocyte tests (PLT) were performed with different HLA-DR mismatched combinations in the presence and absence of cyc losporine A and prednisolone. Differential effects of these immunosuppressi ve drugs were observed. Some reactions could easily be blocked by cyclospor ine alone, whereas others need the addition of high doses of prednisolone a s well before a significant inhibition was found. These differences were no t only found between individual responders but also within one individual d ependent on the stimulatory HLA-antigen involved. When the group of benefic ial mismatches was compared with the group of detrimental mismatches, no di fferences were observed. Our data show that immunosuppressive drugs have a differential effect on in vitro alloimmune responses but these do not diffe rentiate between beneficial and detrimental mismatches as defined by kidney graft survival.