The graft helps to define the character of the alloimmune response

Introduction: In mice, kidney and liver allografts may be spontaneously accepted, whereas cardiac and skin allografts in the same strain combinations are rapidly rejected. The reasons for this dichotomy in murine response outcomes remains to be determined. Methods and results: When DBA/2 (H-2(d)) cardiac allografts were placed in C57BL/6 (H-2(b)) recipients, they were rejected within 10 days, unless the allograft recipients were transiently treated with gallium nitrate (GN), at which time the allografts were accepted for > 150 days. The cardiac allograft rejector mice displayed DBA/2-reactive DTH responses, whereas the cardiac allograft acceptor mice displayed both TGFbeta- and IL10-mediated inhibition of DTH responses. In contrast, DBA/2 kidney allografts placed at the same location in C57BL/6 mice were spontaneously accepted without immunosuppression. These kidney allograft acceptor mice displayed TGFP-mediated, but not IL10-mediated inhibition of donor-reactive DTH responses. Conclusions: In the DBA/2-> C57B1/6 strain combination, cardiac allografts induce pro-inflammatory immunity and allograft rejection, while kidney allografts induce anti-inflammatory immunity and allograft acceptance despite the fact that both organs display the same strong MHC disparities and are implanted at the same location. Anti-inflammatory immunity and allograft acceptance are displayed by cardiac allograft recipients when they are transiently treated with select immunosuppressants. Thus, multiple immune response options are available to the organ allograft recipient, and the choice is determined, to some degree, by the allograft, itself. (C) 2002 Elsevier Science B.V. All rights reserved.