Immunologic Mechanisms of Corneal Allografts Reconstituted from Cultured Allogeneic Endothelial Cells in an Immune-Privileged Site
Immunologic Mechanisms of Corneal Allografts Reconstituted from Cultured Allogeneic Endothelial Cells in an Immune-Privileged Site
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DOI：
10.1167/iovs.08-2530
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Mizuki, Nobuhisa
中科院分区：
文献类型：
--
作者：
Hayashi, Takahiko;Yamagami, Satoru;Mizuki, Nobuhisa
目的.分析培养的角膜内皮细胞（CEC）移植后小鼠模型的结果和免疫学特征。CEC剥夺BALB/c角膜重建在体外与永生化的C3 H-CEC细胞系，然后原位移植到受体BALB/c小鼠与实验性大泡性角膜病变。移植后，在受体小鼠中评价移植物存活率、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、再移植和用C3 H脾细胞免疫后评估CEC移植的命运。与全层角膜移植物的高排斥率不同，由培养的同种异体CEC组成的嵌合CEC同种异体移植物不会引起排斥反应、DTH或混合淋巴细胞反应。从接受嵌合CEC同种异体移植物的小鼠中连续转移脾细胞并没有增加全层角膜移植后的移植物存活率，并且在这些小鼠中第二次全层移植物的排斥率没有改善，这表明没有主动免疫抑制。通过皮下注射与培养的CEC具有相同单倍型的脾细胞的预致敏诱导了对相同同种异体抗原的系统性DTH，但没有促进嵌合CEC同种异体移植物的排斥反应，表明嵌合CEC同种异体移植物被宿主免疫系统忽略。这些结果表明，免疫忽视，而不是积极的免疫抑制是重要的嵌合CEC同种异体移植物的排斥接受。同种异体角膜内皮细胞移植可能是克服术后排斥反应的理想治疗策略。（Invest Ophthalmol维斯科学。2009;50：3151-3158）DOI：10.1167/iovs.08-2530
PURPOSE. To analyze outcomes and immunologic 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 were assessed after adoptive transfer, regrafting, and immunization with C3H splenocytes.RESULTS. 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.CONCLUSIONS. 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. (Invest Ophthalmol Vis Sci. 2009;50:3151-3158) DOI:10.1167/iovs.08-2530