Prolonged blockade of CD40-CD40 ligand interactions by gene transfer of CD40Ig results in long-term heart allograft survival and donor-specific hyporesponsiveness, but does not prevent chronic rejection

摘要: Previous work on blockade of CD40-CD40 ligand interaction in mice and primates with anti-CD40 mAbs has resulted a moderate prolongation allograft survival without the development true tolerance. In this study, we show rats that adenovirus-mediated gene transfer CD40Ig sequences into graft prolonged (>200 days) expression long-term (>300 survival. Recipients expressing displayed strongly (>90%) inhibited mixed leukocyte reactions alloantibody production at early (days 5 17) late time points (>100 day) after transplantation, but showed limited inhibition infiltration cytokine as evaluated by immunohistology (day 5). long-surviving hearts donor-specific hyporesponsiveness since acceptance second cardiac allografts was donor specific. Nevertheless, signs chronic rejection vasculopathy. Occluded vessels infiltration, mainly composed CD4 + CD8 cells, macrophages, mast cells. These recipients also antidonor CTL activity. did not nonspecific immunosuppression, they were able to mount anticognate immune responses partially normal thereafter. We conclude transfer-mediated highly efficient acute heart rats. This treatment induced certain alloreactive mechanisms short-, long-term, which concomitant rejection.