Mechanisms in passive enhancement of cardiac and renal allografts by serum from liver-grafted rats

Abstract

The ability of serum from PVG (haplotype RT1c) rats carrying long-term surviving orthotopic DA (RT1a) liver grafts (OLT serum) to enhance cardiac allografts has been confirmed and extended to renal allografts. One millilitre of OLT serum given at the time of allografting was sufficient to cause permanent acceptance of PVG.RT1a heart or kidney grafts in PVG recipients ('enhanced recipients'); the PVG.RT1a being congenic with respect to PVG, and sharing the RT1a haplotype with DA. Adoptive transfer of thoracic duct lymphocytes (TDL) from rats carrying enhanced liver grafts into irradiated recipients indicated that specific alloreactive clones had been functionally inactivated or deleted; this was accompanied by active suppression in which specific alloreactivity of normal TDL was partially inhibited. In vitro, splenic T cells from rats with enhanced grafts mediated allospecific suppression in mixed lymphocyte reaction (MLR). The serum of rats carrying enhanced grafts was able to specifically suppress MLR of the same donor/recipient combination. Thus enhancement by orthotopic liver transplantation (OLT) serum leads to cellular and serological changes in the recipient associated with maintenance of unresponsiveness. Such changes are similar to those seen in liver graft recipients themselves.