Immunological mechanisms of corneal allografts reconstituted from cultured allogeneic endothelial cells in an immune-privileged site
Takahiko Hayashi 1,
Satoru Yamagami 2*,
Kazumi Tanaka 1,
SEIICHI YOKOO 3,
Tomohiko Usui 4,
Shiro Amano 5,
and
Nobuhisa Mizuki 6
1 Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan
2 Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan; Corneal Regeneration Research Team, Foundation for Biomedical Research and Innovation, Kobe, Japan
3 Corneal Tissue Regeneration, Tokyo University Graduate School of Medicine, Tokyo, Japan
4 Ophthalmology, University of Tokyo, Tokyo, Tokyo, Japan
5 Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Tokyo, Japan
6 Ophthalmology & Visual Science, Yokohama City University, Kanagawa, Japan
* To whom correspondence should be addressed. E-mail: syamagami-tky{at}umin.ac.jp.
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Abstract |
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Purpose. To analyze the outcome and immunological features after cultured corneal endothelial cell (CEC) transplantation in a murine model.
Methods. CEC-deprived BALB/c corneas were reconstituted in vitro with an immortalized C3H-CEC cell line, and then transplanted orthotopically into recipient BALB/c mice with experimental bullous keratopathy. Graft survival rates, donor-specific delayed hypersensitivity (DTH), and mixed lymphocyte reactions were evaluated in recipient mice after grafting. Fates of CEC transplantation was assessed after adoptive transfer, regrafting, and immunization with C3H splenocytes.
Results. Chimeric CEC allografts composed of cultured allogeneic CECs did not provoke any rejection reaction, a weak DTH, and little mixed lymphocyte reactions, unlike the high rejection rate of full-thickness corneal allografts. Adoptive transfer of splenocytes from mice that had accepted chimeric CEC allografts did not increase the graft survival rate after full thickness corneal transplantation and the rejection rate of a second full thickness graft was not improved in these mice, suggestive of no active immune suppression. Pre-sensitization by subcutaneous injection of splenocytes with the same haplotype as cultured CECs induced systemic DTH to the same allogeneic antigens, but did not promote the rejection of chimeric CEC allografts, suggesting that chimeric CEC allografts are ignored by the host immune system.
Conclusions. These findings indicate that immunological ignorance rather than active immune suppression is important for the rejection-free acceptance of chimeric CEC allografts. Transplantation of corneal grafts formed with allogeneic CECs could be an ideal treatment strategy to overcome postoperative rejection.
Key Words:
corneal transplantation, corneal endothelial cells, cell culture
