Renal allograft rejection: examination of adhesion blockade by antilymphocyte antibody drugs.
An assay was developed to investigate the binding of lymphocytes to cultured human renal epithelial cells. This binding was increased following 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 antilymphocyte antibody (ALA) preparations are used frequently to reverse intractable 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-response 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 systems investigated in this work were added to lymphoid cell binding assays. It was found that combinations of these antibodies designed to interfere simultaneously with each of these adhesion interactions inhibited binding less well than the ALA preparation. It is likely that the superior inhibition of binding produced by ALA is due to the polyclonality of the antibodies which can block multiple epitopes on a wide range of potential adhesion molecules.
Department of Surgery, Medical School, University of Newcastle upon Tyne, UK.
J A
JA
Kirby
Y
Y
Lin
D A
DA
Browell
K
K
Clark
B K
BK
Shenton
J L
JL
Forsythe
G
G
Proud
R M
RM
Taylor
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002478:Cells, Cultured; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015815:Cell Adhesion Molecules