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朗格汉斯细胞、原位角膜同种异体移植以及T细胞同种异体识别的直接和间接途径。

Langerhans cells, orthotopic corneal allografts, and direct and indirect pathways of T-cell allorecognition.

作者信息

Sano Y, Ksander B R, Streilein J W

机构信息

Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Invest Ophthalmol Vis Sci. 2000 May;41(6):1422-31.

PMID:10798658
Abstract

PURPOSE

To determine after orthotopic corneal allografting the role of Langerhans cells in activation of T cells via the direct and indirect pathways of allorecognition and the relationship between these pathways and the rapidity of graft rejection.

METHODS

Corneas from eyes of normal mice and from eyes after superficial cauterization were grafted to eyes of major histocompatibility complex (MHC) and/or minor histocompatibility (H)-disparate recipient mice. The grafts were analyzed through time for content of class 1 MHC- bearing Langerhans cells and for rejection or acceptance. Graft recipients were evaluated for acquisition of delayed hypersensitivity (DH) and cytotoxic T cells (Tc) directed at donor MHC and minor H alloantigens.

RESULTS

Langerhans cells migrated more rapidly into epithelium of cauterized grafts than normal grafts. Unlike normal grafts, the vast majority of cauterized allografts were rejected within 2 weeks. Normal grafts induced neither DH nor Tc directed at donor MHC antigens, whereas cauterized grafts induced both DH and Tc specific for donor MHC. All grafts induced DH directed at donor minor H antigens, but only rejected grafts correlated with acquisition of Tc directed at donor minor H antigens. CONCLUSIONS. The rapidity of orthotopic corneal allograft rejection correlated with density of Langerhans cells within epithelium and with acquisition of donor-specific DH and Tc. Although recipient-derived Langerhans cells promoted minor H-specific, self-MHC-restricted T cells (indirect pathway) and subacute graft rejection, donor-derived Langerhans cells promoted early, acute rejection in conjunction with allogeneic MHC-specific Tc (direct pathway).

摘要

目的

确定原位角膜移植后,朗格汉斯细胞在通过同种异体识别的直接和间接途径激活T细胞中的作用,以及这些途径与移植排斥反应速度之间的关系。

方法

将正常小鼠眼睛的角膜和表面烧灼后眼睛的角膜移植到主要组织相容性复合体(MHC)和/或次要组织相容性(H)不相合的受体小鼠眼中。随时间分析移植物中携带1类MHC的朗格汉斯细胞含量以及排斥或接受情况。评估移植物受体针对供体MHC和次要H同种异体抗原获得迟发型超敏反应(DH)和细胞毒性T细胞(Tc)的情况。

结果

与正常移植物相比,朗格汉斯细胞向烧灼移植物上皮的迁移速度更快。与正常移植物不同,绝大多数烧灼的同种异体移植物在2周内被排斥。正常移植物既不诱导针对供体MHC抗原的DH也不诱导Tc,而烧灼的移植物诱导针对供体MHC的DH和Tc。所有移植物均诱导针对供体次要H抗原的DH,但只有被排斥的移植物与针对供体次要H抗原的Tc获得相关。结论。原位角膜移植排斥反应的速度与上皮内朗格汉斯细胞的密度以及供体特异性DH和Tc的获得相关。尽管受体来源的朗格汉斯细胞促进次要H特异性、自身MHC限制的T细胞(间接途径)和亚急性移植排斥,但供体来源的朗格汉斯细胞与同种异体MHC特异性Tc一起促进早期急性排斥(直接途径)。

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