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用于检测肝移植排斥反应过程中肝小叶不同区域浸润 T 细胞空间分布的多重免疫荧光法。

Multiplex Immunofluorescence for Detection of Spatial Distributions of Infiltrating T Cells Within Different Regions of Hepatic Lobules During Liver Transplantation Rejection.

机构信息

Liver Transplantation Center, Clinical Research Center for Pediatric Liver Transplantation, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Clinical Research Center for Pediatric Liver, Transplantation of Capital Medical University, Beijing, 100050, China.

出版信息

Inflammation. 2022 Apr;45(2):651-664. doi: 10.1007/s10753-021-01574-0. Epub 2021 Oct 27.

Abstract

It remains unclear as to whether there are differences that exist in the types and functional status of immune cells within different areas of the liver lobules after rejection of liver transplantation. The composition of infiltrating T cells in liver allografts during liver transplantation rejection is indistinct and difficult to visualize within the same biopsy slide. In an attempt to rectify this problem, we applied multiplex immunofluorescent assays to assess the spatial distribution of various types of infiltrating T cells in different areas of the liver lobules after liver transplantation. In identical areas of the hepatic lobules, the percentage of CD4 T, CD8 T, and regulatory T (Treg) cells in the rejection group was greater than that observed in the non-rejection and normal groups. Within all three groups, the percentage of CD4 T, CD8 T, and Treg cells from the periportal to perivenous zones initially increased and then decreased. In the rejection group, the percentage of CD8 T cells gradually increased from the periportal to perivenous zones, with maximal levels in the perivenous as compared with that in the transitional and periportal zones. In conclusion, levels of CD8 T cells within different regions of liver lobules are closely related to levels of rejection after liver transplantation. Liver transplantation rejection may be linked with increases in CD8 T cells within the perivenous zone. Although the regional percent of increase in CD4 T cells may not reflect level of the rejection, the overall numbers of both of CD4 and CD8 T cells within different regions were closely related to rejection levels.

摘要

目前尚不清楚在肝移植排斥后,肝小叶不同区域内免疫细胞的类型和功能状态是否存在差异。肝移植排斥过程中肝移植肝内浸润 T 细胞的组成不明确,在同一张活检切片内难以可视化。为了解决这个问题,我们应用多重免疫荧光分析来评估肝移植后肝小叶不同区域内各种浸润 T 细胞的空间分布。在肝小叶的相同区域,排斥组中 CD4 T、CD8 T 和调节性 T(Treg)细胞的百分比大于非排斥和正常组观察到的百分比。在所有三组中,CD4 T、CD8 T 和 Treg 细胞从门脉周围区到门静脉区的百分比最初增加,然后减少。在排斥组中,CD8 T 细胞从门脉周围区逐渐增加到门静脉区,与过渡区和门脉周围区相比,门静脉区的水平最高。总之,肝小叶不同区域内的 CD8 T 细胞水平与肝移植后的排斥水平密切相关。肝移植排斥可能与门静脉区 CD8 T 细胞的增加有关。虽然 CD4 T 细胞区域百分比的增加可能不能反映排斥的水平,但不同区域内 CD4 和 CD8 T 细胞的总数与排斥水平密切相关。

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