title: Induction of tolerance to heart allografts in rats using posttransplant total lymphoid irradiation and anti-T cell antibodies.
abstract: This study examined whether posttransplant anti-T cell monoclonal or polyclonal antibody therapy could provide a window of treatment to allow posttransplant total lymphoid irradiation (TLI) to induce tolerance. These experiments were conducted in a high responder strain combination of an ACI cardiac allograft into a Lewis rat. In this situation, treatment with antibody or posttransplant TLI alone is insufficient to induce tolerance, while similar treatments alone have been shown to induce tolerance in low responder strains. The affects of three anti-T cell therapies were compared: anti-CD4 mAb therapy, anti-CD3 mAb, and rabbit antithymocyte globulin (RATG). None of these antibody therapies alone prolonged graft survival indefinitely. Combining anti-CD4 therapy with posttransplant TLI markedly delayed rejection but failed to induce long-term graft survival. Tolerance could be induced by a combination of anti-pan T cell antibody (anti-CD3) and TLI, and, all grafts survived beyond 100 days. RATG failed to prevent graft rejection when used alone or in combination with TLI. However, posttransplant therapy with a combination of RATG, TLI, and single-donor blood transfusion resulted in graft survival beyond 100 days. Recipients bearing long-term donor grafts rejected third-party (PVG) grafts within 2 weeks. Low density donor bone marrow cells used instead of a blood transfusion did not facilitate tolerance. The results indicate that monoclonal or polyclonal anti-pan T cell antibodies, TLI, and a donor blood cell infusion function synergistically in facilitating tolerance to allografts in the posttransplant period.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, California 94305.
authors.forename: S L
authors.initials: SL
authors.lastname: Woodley
authors.forename: K E
authors.initials: KE
authors.lastname: Gurley
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffmann
authors.forename: M R
authors.initials: MR
authors.lastname: Nicolls
authors.forename: R
authors.initials: R
authors.lastname: Hagberg
authors.forename: C
authors.initials: C
authors.lastname: Clayberger
authors.forename: B
authors.initials: B
authors.lastname: Holm
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: B M
authors.initials: BM
authors.lastname: Hall
authors.forename: S
authors.initials: S
authors.lastname: Strober
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001803:Blood Transfusion; D017252:CD3 Complex; D005069:Evaluation Studies as Topic; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D008221:Lymphoid Tissue / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D017252:CD3 Complex