Induction of specific transplantation tolerance via immunisation with donor-directed idiotype(s)

We have re-explored the efficiency of anti-idiotypic immunisation on the generation of transplantation tolerance to cardiac allografts in the rat. Recipient Lewis rats were immunised using 13 different protocols with different doses of anti-DA or anti-BN idiotype(s) and different adjuvants. Four protocols proved successful. Immunisation with Lewis anti-BN blasts either in complete Freund's adjuvant or in muramyl dipeptide (MDP) prolonged the survival of a congeneic AgB incompatible L.BN cardiac allograft from 6.7 +/- 0.3 to 26.8 +/- 5.1 and to greater than 30 +/- 0.0 days, respectively. Immunisation with Lewis anti-T cell 'receptor' in complete Freund's and in MDP increased the survival of a DA heart allograft in Lewis recipients from 6.0 +/- 0.0 days to 13.2 +/- 0.8 and 10.0 +/- 4.0 days, respectively, indicating that most of the MHC effect was also overcome here. The prolongations of survival were immunologically specific, and accompanied by a specific deletion of the relevant alloantibody response. So far no generation of anti-idiotypic antibody in the immunised recipient has been detected; instead, a successful immunisation seems to be accompanied by the generation of immunising idiotype-directed cytotoxic (T?) lymphocytes in the recipient.