IN-VIVO MODULATION OF CD26 (DIPEPTIDYL PEPTIDASE-IV) IN THE MOUSE - EFFECTS OF POLYREACTIVE AND MONOREACTIVE ANTIBODIES

We previously reported that intravenous injections in rabbits or guine a pigs of divalent antibodies to purified protein or carbohydrate anti gens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the in jurious effect of subsequent injection of antibodies (adaptation), ass ociated with shedding of antigen-antibody complexes from endothelial c ells. In the present study, we investigated and compared in mice the e ffects of 3-day multiple injections of two different rabbit antibody ( IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a sing le transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (mon oreactive anti-DPP IV IgG); the second contained antibodies against mu ltiple antigens of the renal tubular brush border (BE), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DP P IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which sho wed loss of DPP IV from cell surface. However, the monoreactive anti-D PP IV IgG induced considerably greater reduction than polyreactive ant i-BE IgG. Loss of DPP IV from the cell surface probably occurred by sh edding of immune complexes into vascular and extravascular fluids, inc luding bile and urine. The results may have relevance to hyperacute re jection of xenografts, as from pigs to primates. Since human natural a ntibodies that bind to porcine cells are polyreactive, a new prophylac tic strategy for hyperacute rejection might be based on down-regulatio n of the major xenogeneic antigen, alpha-galactosyl, by injecting dono r animals with monoreactive alpha-galactosyl antibodies before transpl antation.