New Insights into Prevention of Donor-specific Corneal Graft Rejection
New Insights into Prevention of Donor-specific Corneal Graft Rejection
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预防供体特异性角膜移植排斥的新见解
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Streilein
中科院分区：
文献类型：
--
作者：
J. Yamada;J. Streilein
同种异体角膜移植物放置在“高风险”的人眼预后非常差，甚至密集的全身免疫抑制治疗往往无效。由于角膜移植是人类最常见的临床移植类型，并且由于“高风险”眼睛的角膜移植失败是失明的主要原因，因此了解移植排斥反应的免疫学基础和开发供体特异性抑制是值得研究的目标。在20世纪90年代，发展啮齿类动物模型来实验探索角膜原位移植产生了重要的新知识。由于眼部免疫特权的因素，已经发现次要组织相容性抗原，而不是在主要组织相容性复合体中编码的抗原，是原位角膜移植后最重要的同种免疫启动物。次要的组织相容性抗原由抗原呈递细胞从边缘移植物移植物中呈递给受体免疫系统。从次要组织相容性抗原加工中获得的肽被装载到“自身”MHC分子上，并通过所谓的间接异体识别途径呈递给受体T细胞。现在已经确定，T淋巴细胞（和细胞介导的免疫）而不是抗体（和体液免疫）主要负责啮齿动物角膜原位移植后的破坏性同种免疫。此外，影响延迟型超敏反应的辅助性T细胞1型（而不是CD8细胞毒性T细胞）的CD4 T细胞是角膜移植排斥反应更重要的近似介质。有了这些信息，我们的实验室开发了新的策略来防止角膜移植的排斥反应。我们的希望是，我们将发现对人类有用的供体特异性免疫抑制疗法。
Allogeneic corneal grafts placed in “high-risk” human eyes have a very poor prognosis, and even intensive systemic immunosuppressive therapy is often of no avail. Because corneal transplants are the most common type of clinical grafting performed in humans and because failure of corneal grafts in “highrisk” eyes is a prominent cause of blindness, understanding the immunologic bases of graft rejection and of developing donorspecific suppression are worthy goals for research. The development of rodent models to experimentally explore orthotopic cornea transplants engendered significant new knowledge during the 1990s. Due to the factors responsible for ocular immune privilege, it has been found that minor histocompatibility antigens, rather than antigens encoded within the major histocompatibility complex, are the most important initiators of alloimmunity after orthotopic corneal transplants. Minor histocompatibility antigens are presented to the recipient immune system by antigen-presenting cells that migrate into the graft from the limbus. Peptides derived from processing of minor histocompatibility antigens are loaded onto “self” MHC molecules and presented to recipient T cells by the so-called indirect pathway of allorecognition. It is now established that T lymphocytes (and cell-mediated immunity) rather than antibodies (and humoral immunity) are chiefly responsible for the destructive alloimmunity that follows orthotopic corneal grafting in rodents. Moreover, CD4 T cells of the T helper type 1 phenotype (rather than CD8 cytotoxic T cells) that effect delayedtype hypersensitivity are the more important proximate mediators of corneal graft rejection. Armed with this information, our laboratory has developed novel strategies to prevent rejection of orthotopic corneal transplants. Our hope is that we will discover donor-specific immunosuppressive therapy that will be useful in human beings.
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小鼠原位角膜同种异体移植物排斥后次要同种异体抗原特异性细胞毒性 T 细胞的检测：移植物抗原仅通过“间接途径”识别的证据。
影响因子：
6.2
作者：
Sano,Y;Streilein,JW;Ksander,BR
通讯作者：
Ksander,BR
MHC 抗原在小鼠眼组织中的分布和个体发育。
影响因子：
4.4
作者：
Wang,HM;Kaplan,HJ;Chan,WC;Johnson,M
通讯作者：
Johnson,M
人角膜细胞表达 HLA 抗原。
影响因子：
4.2
作者：
Treseler,PA;Foulks,GN;Sanfilippo,F
通讯作者：
Sanfilippo,F
白介素 1 受体拮抗剂可抑制角膜移植中的异体敏化。
DOI：
10.1001/archopht.116.10.1351
发表时间：
1998
期刊：
Archives of ophthalmology (Chicago, Ill. : 1960)
影响因子：
--
作者：
Yamada,J;Dana,MR;Zhu,SN;Alard,P;Streilein,JW
通讯作者：
Streilein,JW
影响因子：
13.7
作者：
Thomas E. Gillette;John W. Chandler;Jack V. Greiner
通讯作者：
Thomas E. Gillette;John W. Chandler;Jack V. Greiner