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抗 LAP 单克隆抗体下调 CD4+LAP+T 细胞对小鼠同种异体角膜移植的影响。

The Effects of Anti-LAP Monoclonal Antibody Down-regulation of CD4+LAP+ T Cells on Allogeneic Corneal Transplantation in Mice.

机构信息

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmic and Visual Science Key Lab, Beijing, China.

Department of Ophthalmology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.

出版信息

Sci Rep. 2018 May 22;8(1):8021. doi: 10.1038/s41598-018-26235-5.

DOI:10.1038/s41598-018-26235-5
PMID:29789580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5964070/
Abstract

CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN-γ+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-γ, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-β1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes.

摘要

CD4+潜伏期相关肽 (LAP)+T 细胞是一种新发现的具有抑制免疫反应功能的 T 细胞亚群。在这项研究中，我们通过使用抗 LAP mAb 下调其表达来研究 CD4+LAP+T 细胞在小鼠角膜同种异体移植物存活中的作用。我们发现，阻断 LAP 导致接受角膜同种异体穿透移植的小鼠淋巴结和脾脏中表达 CD4+Foxp3+、CD4+GARP+、CD4+LAP+和 CD4+IL-10+的 T 细胞比例下降，但不影响角膜移植物存活。此外，在排斥角膜移植物的小鼠中，淋巴结和脾脏中 CD4+IFN-γ+和 CD4+IL-17A+T 细胞的百分比以及房水中 TNF、IFN-γ、IL-17A 和 IL-6 的水平显著增加。在角膜排斥期间，TGF-β1 在角膜移植物中的表达减少。因此，抗 LAP mAb 可能通过其免疫抑制作用下调调节性 T 细胞亚群。角膜移植物的排斥似乎主要与外周淋巴结中 Th1 和 Th17 细胞亚群的上调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/42b4d91701c3/41598_2018_26235_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/be89e5a1c29a/41598_2018_26235_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/6a682a1ce557/41598_2018_26235_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/bdc5fd728e1f/41598_2018_26235_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/89875c1bdb8b/41598_2018_26235_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/42b4d91701c3/41598_2018_26235_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/be89e5a1c29a/41598_2018_26235_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/6a682a1ce557/41598_2018_26235_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/bdc5fd728e1f/41598_2018_26235_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/89875c1bdb8b/41598_2018_26235_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/597b/5964070/42b4d91701c3/41598_2018_26235_Fig5_HTML.jpg

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本文引用的文献

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Impaired Function of Peripherally Induced Regulatory T Cells in Hosts at High Risk of Graft Rejection.外周诱导调节性 T 细胞功能障碍与移植排斥高风险宿主。
Sci Rep. 2016 Dec 23;6:39924. doi: 10.1038/srep39924.
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Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients.将FoxP3和Helios与GARP/LAP标志物相结合，能够识别癌症患者中扩增的调节性T细胞亚群。
免疫细胞多样性和异质性在角膜移植存活中的作用：一项系统评价和荟萃分析
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