Document 0023
 DOCN  M9580023
 TI    Tolerance induced by direct inoculation of donor antigen into the thymus
       in low and high responder rodents.
 DT    9506
 AU    Alfrey EJ; Wang X; Lee L; Holm B; Kim J; Adams G; Dafoe DC; Department
       of Surgery, School of Medicine, Stanford University,; California 94305,
       USA.
 SO    Transplantation. 1995 Apr 27;59(8):1171-6. Unique Identifier : AIDSLINE
       MED/95250172
 AB    A novel approach to tolerance induction in rats was recently described
       where donor antigen is inoculated directly into the thymus along with a
       brief period of immunosuppression in a pretransplant strategy. To
       develop a strategy that has more clinical appeal, we evaluated the
       timing of donor antigen inoculation in relation to allografting, the use
       of frozen bone marrow as the antigen, and the dose response of purified
       T cells as the antigen in a low responder heterotopic heart allograft
       combination. Additionally, the success of this pretransplant strategy in
       different low and high responder strain combinations was defined. In
       tolerant low responder animals we evaluated in vitro and in vivo
       cellular immunity. Tolerant host strain naive CD8+ T cell responses to
       donor and third party stimulators were compared to determine if
       tolerance is related to the strength of the response of the T cell
       subsets to donor antigen. Frozen bone marrow can induce tolerance in a
       low responder combination. Additionally, the dose of purified T cells
       necessary for tolerance induction was 5 x 10(5) cells. The pretransplant
       strategy was successful in two low responder strain combinations, Lewis
       into Wistar Furth and Lewis into DA, but unsuccessful in all high
       responder strain combinations evaluated. Low responder animals
       unresponsive to donor heart allografts demonstrate intact cell-mediated
       immunity and donor-specific tolerance in vivo by rejecting third party
       but not second donor strain hearts. The in vitro responses of tolerant
       animals demonstrated donor-specific suppression of the MHC class II
       response but an intact (normal) response to third party stimulators by
       proliferation assays and IFN-gamma production, suggesting suppression at
       the CD4+ T cell subset level.
 DE    Animal  Bone Marrow Transplantation/*IMMUNOLOGY/METHODS  Comparative
       Study  CD8-Positive T-Lymphocytes/IMMUNOLOGY  Graft Rejection/IMMUNOLOGY
       Heart Transplantation/*IMMUNOLOGY  Histocompatibility Antigens Class
       II/BIOSYNTHESIS  Immunity, Cellular  Immunosuppression/*METHODS
       Interferon Type II/BIOSYNTHESIS  Rats  Rats, Inbred BUF  Rats, Inbred
       Lew  Rats, Inbred Strains  Rats, Inbred WF  Species Specificity
       Support, Non-U.S. Gov't  T-Lymphocyte Subsets/IMMUNOLOGY  Thymus
       Gland/*IMMUNOLOGY  Transplantation, Homologous  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).