Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy.

Academic Article

Abstract

  • Tolerance induction can prevent acute kidney allograft rejection without chronic immunosuppression. It is uncertain whether specific tolerance can prevent chronic allograft nephropathy (CAN), which involves both nonimmune and immune injury. This report provides evidence that immunologically tolerant macaques, induced with immunotoxin and deoxyspergualin, developed neither acute rejection nor CAN. Long survivors, bearing MHC-mismatched grafts without chronic immunosuppression for 0.8 to 3.4 years, exhibited general immune competence with donor-specific T and B cell tolerance and no functional or histological evidence of CAN. Stringent criteria for tolerance were satisfied by specific prolongation of donor skin grafts with rapid rejection of third-party skin, followed by indefinite acceptance of a second donor kidney graft and establishment of microchimerism. Primate tolerance with documented absence of CAN may give impetus to the clinical application of tolerance.
  • Published In

  • Transplantation  Journal
  • Keywords

  • Animals, B-Lymphocytes, CD3 Complex, Chronic Disease, Guanidines, Immune Tolerance, Immunoglobulin G, Immunosuppressive Agents, Immunotoxins, Kidney, Kidney Diseases, Kidney Transplantation, Macaca mulatta, Male, T-Lymphocytes, Transplantation, Homologous
  • Author List

  • Thomas JM; Eckhoff DE; Contreras JL; Lobashevsky AL; Hubbard WJ; Moore JK; Cook WJ; Thomas FT; Neville DM
  • Start Page

  • 2497
  • End Page

  • 2503
  • Volume

  • 69
  • Issue

  • 12