Recombinant IFN-gamma abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

Donor-specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor-specific blood transfusion (DST). We previously showed t hat this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount a n efficient anti-donor humoral response whereas transfer of sera from rejec ting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post-graft administration of recombinant IFN-gamma (rIF N-gamma). To elucidate the mechanisms of action of rIFN-gamma, T cell, macr ophage and B cell functions were assessed in allograft recipients. IFN-gamm a did not restore the expression of Th1-related cytokine mRNA or the activa ted macrophage product inducible nitric oxide synthase in allografts. Impor tantly, rIFN-gamma treatment promptly restored the anti-donor humoral respo nse in DST-treated recipients. We conclude that rIFN-gamma treatment in DST -treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help f or IgG alloantibody production which is lacking in these animals.