INHIBITION OF ALLOGRAFT-REJECTION BY ANTI-T-CELL RECEPTOR-ALPHA-BETA MONOCLONAL-ANTIBODIES PRESERVING RESISTANCE TO BACTERIAL-INFECTION

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical o rgan transplantation to reverse acute allograft rejection; however, se vere immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppress ing allograft rejection while preserving resistance to opportunistic i nfections. In this study, we compared the effects of the in vivo admin istration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57 -597, with those of anti-CD3 mAb, 145-2C11 . Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin graft ing led to a longer allograft survival than that of anti-CD3 mAb at an y of the comparable dosages examined. In the lymphoid organs of mice t reated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remai ned al a relatively increased level on day 14 after anti-TcR alpha bet a mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functional ly intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR a lpha beta mAb, which partially preserved anti-bacterial resistance, ma y be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these r esults also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribut e to allograft rejection in vivo.