RENAL-ALLOGRAFT REJECTION - EXAMINATION OF ADHESION BLOCKADE BY ANTILYMPHOCYTE ANTIBODY DRUGS

An assay was developed to investigate the binding of lymphocytes to cu ltured human renal epithelial cells. This binding was increased follow ing lymphocyte activation by culture either with a polyclonal mitogen or with allogeneic stimulator cells. It was shown that such activation increased lymphocyte expression of the adhesion molecules CD2, LFA-1, and VLA-4. The ligand for each of these molecules was demonstrated on the surface of cultured renal epithelial cells. Polyclonal antilympho cyte antibody (ALA) preparations are used frequently to reverse intrac table episodes of acute renal allograft rejection. It was demonstrated that such agents reduce the binding of activated lymphocytes to renal epithelial cells and subsequent cell lysis with a similar dose-respon se curve. Application of this assay may allow improved evaluation and titration of therapeutic antibody preparations. A range of monoclonal antibodies specific for components of the three adhesion molecule syst ems investigated in this work were added to lymphoid cell binding assa ys. It was found that combinations of these antibodies designed to int erfere simultaneously with each of these adhesion interactions inhibit ed binding less well than the ALA preparation. It is likely that the s uperior inhibition of binding produced by ALA is due to the polyclonal ity of the antibodies which can block multiple epitopes on a wide rang e of potential adhesion molecules.