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Related Experiment Videos

Tolerance in a concordant nonhuman primate model.

A M Bartholomew1, J Powelson, D H Sachs

  • 1Transplantation Unit of the General Surgical Service, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston 02114, USA.

Transplantation
|December 28, 1999
PubMed
Summary
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Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach.

Human immunology·2017

Inducing mixed lymphohematopoietic chimerism can lead to donor-specific renal xenograft tolerance in nonhuman primates. Adding 15-deoxyspergualine extended survival, but antibody-mediated rejection remained a challenge.

Area of Science:

  • Transplantation immunology
  • Xenotransplantation research
  • Immunosuppression strategies

Background:

  • Previous studies showed mixed lymphohematopoietic chimerism induces donor-specific renal allograft tolerance in nonhuman primates without chronic immunosuppression.
  • This study investigated if similar tolerance could be achieved for baboon-to-cygnus renal xenografts.

Purpose of the Study:

  • To determine the efficacy of mixed lymphohematopoietic chimerism in inducing tolerance for renal xenografts.
  • To evaluate the impact of adding 15-deoxyspergualine on xenograft survival and immune response.

Main Methods:

  • Nonhuman primates received preconditioning (anti-thymocyte globulin, total body irradiation, thymic irradiation), splenectomy, native nephrectomies, and baboon marrow and renal transplants.
  • Postoperative cyclosporine was administered for 28 days, with 15-deoxyspergualine added in one group.

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Main Results:

  • Group 1 animals exhibited rapid xenograft failure due to anti-donor antibodies and humoral rejection.
  • Group 2, treated with 15-deoxyspergualine, showed extended survival, with one animal developing transient donor-specific hyporesponsiveness.
  • A subsequent donor-specific skin graft in a long-term survivor triggered anti-donor antibody production and xenograft rejection.

Conclusions:

  • Antibody-mediated rejection is a significant barrier in concordant xenografts compared to allografts.
  • 15-deoxyspergualine administration for two weeks post-transplant improved xenograft survival up to six months.
  • Unlike allografts, xenograft acceptance in this model was disrupted by a donor-specific skin graft challenge.