ALLOANTIBODY AND INTRAGRAFT CELLULAR-RESPONSE TO MHC CLASS-I DISPARATE KIDNEY ALLOGRAFTS IN RECIPIENTS TOLERIZED BY DONOR-SPECIFIC TRANSFUSION AND CYCLOSPORINE

Congenic PVG.RT1(u) rats rapidly reject A(a) class I-disparate kidney allografts from recombinant PVG R8 donors and we recently demonstrated that anti-class I MHC alloantibody plays a critical role in effecting acute rejection in this experimental model, In this article, we show that PVG.RT1(u) recipients can be rendered permanently and specificall y tolerant to R8 kidney allografts by administration of four weekly do nor-specific transfusions (DST) combined with a 7-day course of cyclos porine given with the first DST, Tolerance induction correlated with a brogation of a cytotoxic alloantibody response by thymus-independent, i.e., peripheral mechanisms; IgM and all IgG subclasses of anti-class I alloantibody were abolished. In contrast, nonrejecting kidney allogr afts in tolerant rats and rejecting grafts from unmodified recipients were similarly infiltrated by mononuclear cells, and intragraft transc ripts for interleukin (IL)-2, interferon-gamma, and IL-13 were readily detected by reverse transcriptase polymerase chain reaction with no a pparent quantitative difference between the two groups, Messenger RNA for IL-4 and IL-10 was present in rejecting grafts but barely detectab le in grafts from tolerant animals. These results suggest that toleran ce induction by DST and cyclosporine is, in this experimental model, a ssociated with a selective impairment in humoral alloimmunity.