NONSPECIFIC MIXED LYMPHOCYTE CULTURE INHIBITORY ANTIBODIES IN SERA OFTOLERANT TRANSPLANTED BABOONS CONDITIONED WITH TOTAL LYMPHOID IRRADIATION

Pretransplant conditioning of baboons with total lymphoid irradiation allows long-term renal allograft acceptance in one third of the recipi ents. Brief additional immunosuppression was given to some animals, bu t always for less than 14 days after transplant. This enabled us to st udy mechanisms of graft tolerance in the absence of long-term, nonspec ific drug immuno-suppression. While 3 patterns of unresponsiveness wer e noted, this study concentrated on serum-mediated suppression. Eleven of 16 (69%) baboons destined to become tolerant to their grafts devel oped a nonspecific MLC inhibitory factor in their sera. In most animal s it appeared within 3-5 weeks after transplantation and persisted ove r the period of study (91-793 days after Tx). The suppressor factor wa s absent in sera from 38 control animals and 8/9 rejectors. It was sho wn to be a low affinity IgG antibody that inhibited MLC by binding to stimulator cells, an effect that could be overcome by addition of rIL- 2 to cultures. NK cell lysis, cell-mediated lympholysis, and polyclona l mitogenesis were unaffected. Antibody binding to purified baboon T c ells could not be demonstrated, though binding to EBV-transformed B ce lls was readily shown. Our study shows that total lymphoid irradiation permits the generation of blocking antibodies directed against APCs a s one mechanism of maintaining T cell unresponsiveness. These observat ions are consistent with the masking of ligands involved in antigen pr esentation or costimulation leading to a sustained state of autoenhanc ement.