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Primate renal transplants using immunotoxin

S J Knechtle1, J H Fechner, Y Dong

  • 1Department of Surgery, University of Wisconsin, Madison, USA.

Surgery
|August 26, 1998
PubMed
Summary
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Starting immunotoxin therapy on transplant day prolongs renal allograft survival in monkeys. However, interstitial nephritis and chronic rejection impede long-term tolerance, while T-cell responses remain intact.

Area of Science:

  • Transplantation immunology
  • Immunotherapy
  • Renal allografts

Background:

  • T-lymphocyte depletion using immunotoxin FN 18-CRM9 prior to transplantation induced tolerance.
  • Previous studies showed tolerance with T-lymphocyte depletion 7 days before renal allograft transplantation.
  • This study investigates immunotoxin administration on the day of transplantation.

Purpose of the Study:

  • To evaluate the efficacy of immunotoxin FN 18-CRM9 when initiated on the day of renal transplantation.
  • To assess the impact on rhesus monkey and allograft survival.
  • To determine effects on antibody production and T-cell recovery.

Main Methods:

  • Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys.

Related Experiment Videos

  • Immunotoxin was administered on the day of transplantation, with or without supportive immunosuppression (prednisone, mycophenolate mofetil).
  • Flow cytometry analyzed T-cell subsets and alloantibody levels; immune responses to tetanus, diphtheria, and xenoantigens were assessed.

    • Main Results:

    • Initiating immunotoxin on transplant day significantly prolonged allograft survival across all groups.
    • Graft loss was primarily attributed to interstitial nephritis (days 50-135) and chronic rejection (later).
    • Monkeys maintained intact antibody responses, and CD4+ T-cell counts gradually recovered over six months.

    Conclusions:

    • Immunotoxin administration on transplant day reliably extends renal allograft survival.
    • Interstitial nephritis and chronic rejection are significant barriers to achieving long-term tolerance.
    • T-cell-dependent B-cell immune responses remain functional following this immunotoxin treatment regimen.