title: 'Chimeric' grafts assembled from multiple allodisparate donors enjoy enhanced transplant survival.
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]-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.
authors.affiliation: Schepens Eye Research Institute, Boston, MA, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Saban
authors.forename: S K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: El Annan
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: R
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D016039:Corneal Transplantation / Q000276:immunology*; D004727:Endothelium / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007371:Interferon-gamma