THE ASSOCIATION OF ENHANCEMENT OF RENAL-ALLOGRAFT SURVIVAL BY DONOR-SPECIFIC BLOOD-TRANSFUSION WITH HOST MHC-LINKED INHIBITION OF IGG ANTIDONOR CLASS-I ALLOANTIBODY RESPONSES

Donor-specific blood transfusion (DSBT) in animals and humans can eith er promote subsequent renal graft survival or lead to sensitization an d graft rejection. Using a rat renal allograft model, we have examined whether the effects of DSBT on renal allograft outcome and IgG alloan tibody responses are linked to the host MHC. In F1 rats produced by ma ting PVG (RT1c), a low IgG alloantibody responder to transfused ACI (R T1a) blood, with 3 different high-IgG responders [W/F (RT1u), LOU (RT1 u), and LEW (RT1(1))], high IgG alloantibody production was found to b e inherited as a dominant trait and associated with acute rejection of ACI renal allografts. DSBT given to offspring of (PVGXW/F)F1 rats bac kcrossed to W/F with either RT1u//c (u/c) or RT1u/u) (u/u) phenotype i nduced high-IgG-alloantibody responses that were associated with acute renal allograft rejection. Likewise, offspring of (PVGXW/F)F1 rats ba ckcrossed to PVG expressing the u/c phenotype had high IgG responses t o ACI DSBT associated with acute renal allograft rejection. In contras t, DSBT given to backcrossed recipients expressing the RT1c/c (c/c) ph enotype elicited a transient IgM response that switched to a very low IgG response and was associated with renal allograft acceptance. Analy sis of IgG isotypes demonstrated that DSBT prevented production of IgG 1 and IgG2a, and to a lesser extent IgG2b and IgG2c alloantibodies in c/c but not u/c renal allograft recipients. The differences in the lev el and isotype of IgG alloantibody responses found in sera of DSBT-pre treated backcross rats of u/c and c/c phenotypes were also present in allograft eluates and splenocyte cultures. Likewise, DSBT-pretreated r enal allograft recipients of the c/c phenotype produced lower levels o f alloantibodies directed to class I RT1.A(a) antigens compared with t heir u/c counterparts; in contrast, no difference was found in alloant ibody responses to class II RT1.B(a) antigens. These findings demonstr ate that the variable ability of DSBT to enhance renal allograft survi val correlates with the inhibition of antidonor class I alloantibody r esponses of all IgG subclasses by a mechanism that is linked to host M HC.