Prolonged survival of renal allografts in outbred rabbits treated with donor specific F(ab')2 alloantibody.

Renal allograft survival was prolonged in rabbits, a species in which antibody mediated hyperacute rejection can occur, by administering large quantities of donor specific F(ab')(2) alloantibody. In 13 control animals, onset of uremia with histological evidence of rejection occurred at a mean of 6.0 days. Eight of eight rabbits actively immunized and seven of nine rabbits passively immunized with unmodified donor specific IgG alloantibody hyperacutely rejected an allografted kidney. Four rabbits treated with non-specific F(ab')(2) for one week acutely rejected an allografted kidney at a mean of 6.2 days. In 12 recipient rabbits receiving 100-500 mg of donor specific F(ab')(2) alloantibody for a mean of 8.5 days, onset of uremia was delayed to a mean of 14.5 days following transplantation. Recipients were selected so that the donor specific F(ab')(2) alloantibody employed had no activity against recipient antigens. This selection maximized the antigenic difference between the donor and recipient, and also assured us that the donor specific F(ab')(2) was directed against antigens present in the donor but absent in the recipient. Passive administration of donor specific F(ab')(2) allowed antibody mediated suppression of a specific immune response to occur without risk of hyperacute rejection. However, the onset of rejection could not be delayed indefinitely by this treatment. The experimental conditions employed and the difficulties encountered closely resemble those which will occur for clinical utilization of passive immunological enhancement.