Murine orthotopic corneal transplantation in high-risk eyes. Rejection is dictated primarily by weak rather than strong alloantigens

Invest Ophthalmol Vis Sci. 1997 May;38(6):1130-8.

Abstract

Purpose: Using a model of orthotopic corneal transplantation in which allografts were placed in normal eyes of mice, the authors previously reported that grafts bearing minor H antigens alone are more likely to be rejected (approximately 50%) than are grafts displaying only major histocompatibility (MHC) alloantigens (20%). These studies have been extended to include corneal grafts placed in neovascularized high-risk eyes of recipient mice.

Methods: Neovascularization was induced by placing sutures in the central cornea of one eye of recipient mice. Two weeks later, MHC class I only, class II only, minor H only, or MHC+minor H disparate corneas were grafted into these sutured eyes, and their rejection rates were examined.

Results: Although MHC+minor H disparate corneal allografts were rejected uniformly in neovascularized graft beds in 12 (100%) of 12, MHC class I only disparate grafts were rejected in 8 (66.7%) of 12 and MHC class II only disparate corneal allografts were rejected in 7 (58.3%) of 12. Surprisingly, the rejection rate of minor H only disparate corneal allografts was 10 (90.9%) of 11.

Conclusions: These findings indicate that for orthotopic corneal allografts placed in high-risk graft beds, minor H antigens offer a more formidable barrier to graft acceptance than do MHC-encoded antigens. The authors speculate that this unexpected outcome may reflect a reduced level of MHC expression on corneal tissue. Moreover, because the cornea as a graft lacks bone marrow-derived dendritic cells, allorecognition by recipient T cells must occur by way of the indirect pathway of alloantigen processing, and in this situation, minor H antigens may compete favorably with MHC antigens for presentation by recipient antigen-presenting cells that infiltrate the graft.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cornea / surgery
  • Corneal Transplantation*
  • Graft Rejection / immunology*
  • Graft Survival
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Isoantigens / immunology*
  • Mice
  • Mice, Inbred Strains
  • Minor Histocompatibility Antigens / immunology
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / surgery
  • Risk Factors
  • Sutures

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Isoantigens
  • Minor Histocompatibility Antigens