'Chimeric' grafts assembled from multiple allodisparate donors enjoy enhanced transplant survival

D. R. Saban, S. K. Chauhan, X. Zhang, J. El Annan, Y. Jin, R. Dana

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium - which shares the same alloantigens - is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such 'chimeric' allografts consisted of a C3H/He (H-2 k) corneal epithelium over a C57BL/6 (H-2 b) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2 d) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4 + interferon [IFN]-γ +) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds.

Original languageEnglish (US)
Pages (from-to)473-482
Number of pages10
JournalAmerican Journal of Transplantation
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2009

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Keywords

  • Allograft rejection
  • Allosensitization
  • Corneal allograft
  • Immune regulation
  • Th1
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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