May 1997
Volume 38, Issue 6
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Articles  |   May 1997
Murine orthotopic corneal transplantation in high-risk eyes. Rejection is dictated primarily by weak rather than strong alloantigens.
Author Affiliations
  • Y Sano
    Schepens Eye Research Institute, Boston, MA 02114, USA.
  • B R Ksander
    Schepens Eye Research Institute, Boston, MA 02114, USA.
  • J W Streilein
    Schepens Eye Research Institute, Boston, MA 02114, USA.
Investigative Ophthalmology & Visual Science May 1997, Vol.38, 1130-1138. doi:
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      Y Sano, B R Ksander, J W Streilein; Murine orthotopic corneal transplantation in high-risk eyes. Rejection is dictated primarily by weak rather than strong alloantigens.. Invest. Ophthalmol. Vis. Sci. 1997;38(6):1130-1138.

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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.

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