IMMUNOLOGICAL APPROACH TO INHIBIT FORMATION OF ANTI-ANTIBODIES TO ALLOGENEIC AND XENOGENEIC ANTI-T-CELL IMMUNOGLOBULIN

Inhibitory anti-antibodies induced in patients by xenogeneic or even b y humanized anti-T cell antibodies remain an unresolved problem. Mice also produce anti-antibodies following injection of xeno- or allogenei c anti-T cell antibodies. Here we report a principle based on sequenti ally applied anti-T cell antibodies generated in different species, wh ich results in suppressed anti-antibody formation and prolonged immuno suppression. Thus, a single priming injection in mice of mouse (MmT1 o r MmT5 differing by idiotype only) or of rat (RmT1) anti-mouse Thy-1 m onoclonal antibodies (mAb) or of rat anti-mouse L3T4 + Ly-2 (RmCD4 + C D8) mAb suppressed anti-antibody formation against subsequent booster injections of one of the above antibodies, provided that they differed in species origin from the priming antibody. Correspondingly, a sixfo ld and longer prolongation of 50% survival of fully mismatched skin gr afts was observed. Less or no anti-antibody suppression and little pro longation of graft surival was obtained if the 'first' and the 'second ' (and following) antibody injections were of the same species, differ ing by iso- or idiotype only. Finally, the suppressive principle did n ot manifest itself at all if the initial antibody injection included b oth the first and second antibody. These findings are discussed with r eference to earlier studies on hapten/carrier effects as well as on im munosuppression attributed to 'non-depleting' rat anti-CD4/CD8 T cell antibodies.