Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine

Joshua D. Mezrich, Louis C. Benjamin, Jessica A. Sachs, Stuart L. Houser, Parsia A. Vagefi, David H. Sachs, Joren C. Madsen, Kazuhiko Yamada

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. Methods. Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n = 5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n = 2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n = 2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n = 2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n = 4). Results. Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. Conclusions. Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.

Original languageEnglish (US)
Pages (from-to)1663-1673
Number of pages11
JournalTransplantation
Volume79
Issue number12
DOIs
StatePublished - Jun 27 2005
Externally publishedYes

Fingerprint

Miniature Swine
Thymus Gland
Maintenance
Transplants
Kidney
Allografts
Nephrectomy
Kidney Transplantation
Skin
Transplantation
Thymectomy
Heart Transplantation
Major Histocompatibility Complex

Keywords

  • Anergy
  • Cytotoxic T lymphocyte
  • Major histocompatibility complex
  • Suppression
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Mezrich, J. D., Benjamin, L. C., Sachs, J. A., Houser, S. L., Vagefi, P. A., Sachs, D. H., ... Yamada, K. (2005). Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine. Transplantation, 79(12), 1663-1673. https://doi.org/10.1097/01.TP.0000160679.04441.B7

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine. / Mezrich, Joshua D.; Benjamin, Louis C.; Sachs, Jessica A.; Houser, Stuart L.; Vagefi, Parsia A.; Sachs, David H.; Madsen, Joren C.; Yamada, Kazuhiko.

In: Transplantation, Vol. 79, No. 12, 27.06.2005, p. 1663-1673.

Research output: Contribution to journalArticle

Mezrich, JD, Benjamin, LC, Sachs, JA, Houser, SL, Vagefi, PA, Sachs, DH, Madsen, JC & Yamada, K 2005, 'Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine', Transplantation, vol. 79, no. 12, pp. 1663-1673. https://doi.org/10.1097/01.TP.0000160679.04441.B7
Mezrich, Joshua D. ; Benjamin, Louis C. ; Sachs, Jessica A. ; Houser, Stuart L. ; Vagefi, Parsia A. ; Sachs, David H. ; Madsen, Joren C. ; Yamada, Kazuhiko. / Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine. In: Transplantation. 2005 ; Vol. 79, No. 12. pp. 1663-1673.
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AU - Vagefi, Parsia A.

AU - Sachs, David H.

AU - Madsen, Joren C.

AU - Yamada, Kazuhiko

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AB - Background. The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. Methods. Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n = 5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n = 2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n = 2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n = 2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n = 4). Results. Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. Conclusions. Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.

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