Evidence for a gene controlling the induction of transplantation tolerance

P. W. Lee, J. S. Hanekamp, V. Villani, P. A. Vagefi, R. A. Cina, C. Kamano, P. E. O'Malley, S. Arn, K. Yamada, D. H. Sachs

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Class I mismatched kidney transplantation in Massachusetts General Hospital MHC-defined miniature swine has been studied extensively as a model for induction of systemic allograft tolerance. In a large series of juvenile swine, long-term graft acceptance has been observed consistently following a 12-day course of cyclosporine. It was therefore surprising when three of five recipients in one of our studies rejected their grafts. Examination of the origins of the rejecting animals revealed that they were derived from a subline of the SLAdd miniature swine herd that was intentionally being inbred toward full homozygosity and had been inbred for eight generations prior to these experiments. A blinded study of additional class I mismatched renal transplants into animals from this subline confirmed the genetic basis of this rejection. We present here preliminary evidence suggesting that a likely explanation for this phenomenon is that the rejectors in this subline are homozygous for a recessive mutant allele of a gene normally involved in the induction of tolerance. Subsequent studies will be directed toward identification and characterization of the gene(s) involved, since existence of a similar genetic locus in humans might have implications for assessing an individual's likelihood of graft rejection versus tolerance induction prior to organ transplantation.

Original languageEnglish (US)
Pages (from-to)952-959
Number of pages8
JournalAmerican Journal of Transplantation
Volume14
Issue number4
DOIs
StatePublished - Apr 2014
Externally publishedYes

Keywords

  • MGH miniature swine
  • MHC
  • thymus
  • tolerance/suppression/anergy
  • transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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