Nonspecific mixed lymphocyte culture inhibitory antibodies in sera of tolerant 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 recipients. Brief additional immunosuppression was given to some animals, but always for less than 14 days after transplant. This enabled us to study mechanisms of graft tolerance in the absence of long-term, nonspecific drug immunosuppression. While 3 patterns of unresponsiveness were noted, this study concentrated on serum-mediated suppression. Eleven of 16 (69%) baboons destined to become tolerant to their grafts developed a nonspecific MLC inhibitory factor in their sera. In most animals it appeared within 3-5 weeks after transplantation and persisted over the period of study (91-793 days after Tx). The suppressor factor was absent in sera from 38 control animals and 8/9 rejectors. It was shown 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 polyclonal mitogenesis were unaffected. Antibody binding to purified baboon T cells could not be demonstrated, though binding to EBV-transformed B cells was readily shown. Our study shows that total lymphoid irradiation permits the generation of blocking antibodies directed against APCs as one mechanism of maintaining T cell unresponsiveness. These observations are consistent with the masking of ligands involved in antigen presentation or costimulation leading to a sustained state of autoenhancement.
Stark
J H
JH
Department of Surgery, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Smit
J A
JA
Myburgh
J A
JA
D000818:Animals; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D001667:Binding, Competitive; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008297:Male; D010215:Papio / Q000097:blood* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; D007376:Interleukin-2; D011994:Recombinant Proteins