Hayashi Takahiko, Yamagami Satoru, Tanaka Kazumi, Yokoo Seiichi, Usui Tomohiko, Amano Shiro, Mizuki Nobuhisa
Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3151-8. doi: 10.1167/iovs.08-2530. Epub 2009 Feb 28.
To analyze outcomes and immunologic features after cultured corneal endothelial cell (CEC) transplantation in a murine model.
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 were assessed after adoptive transfer, regrafting, and immunization with C3H splenocytes.
Chimeric CEC allografts composed of cultured allogeneic CECs did not provoke rejection reaction, DTH, or mixed-lymphocyte reactions, unlike the high rejection rate that occurred in 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 immunosuppression. 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.
These findings indicate that immunologic ignorance rather than active immunosuppression 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.
分析在小鼠模型中培养的角膜内皮细胞（CEC）移植后的结果及免疫特征。
用永生化的C3H - CEC细胞系在体外重建CEC缺失的BALB/c角膜，然后原位移植到患有实验性大疱性角膜病变的受体BALB/c小鼠体内。移植后评估受体小鼠的移植物存活率、供体特异性迟发型超敏反应（DTH）和混合淋巴细胞反应。在过继转移、再次移植并用C3H脾细胞免疫后评估CEC移植的命运。
与全层角膜同种异体移植中出现的高排斥率不同，由培养的同种异体CEC组成的嵌合CEC同种异体移植未引发排斥反应、DTH或混合淋巴细胞反应。接受嵌合CEC同种异体移植的小鼠的脾细胞过继转移并未提高全层角膜移植后的移植物存活率，并且这些小鼠中第二次全层移植物的排斥率也未改善，提示无主动免疫抑制。皮下注射与培养的CEC具有相同单倍型的脾细胞进行预致敏可诱导对相同同种异体抗原的全身性DTH，但并未促进嵌合CEC同种异体移植的排斥，这表明嵌合CEC同种异体移植被宿主免疫系统忽视。
这些发现表明，免疫忽视而非主动免疫抑制对于嵌合CEC同种异体移植的无排斥接受很重要。用同种异体CEC形成的角膜移植物移植可能是克服术后排斥的理想治疗策略。
