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

Published

Journal Article

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]-gamma(+)) 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.

Full Text

Duke Authors

Cited Authors

  • Saban, DR; Chauhan, SK; Zhang, X; El Annan, J; Jin, Y; Dana, R

Published Date

  • March 2009

Published In

Volume / Issue

  • 9 / 3

Start / End Page

  • 473 - 482

PubMed ID

  • 19260831

Pubmed Central ID

  • 19260831

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2008.02535.x

Language

  • eng

Conference Location

  • United States