Anti-Tim-1 monoclonal antibody (mAb) RMT1-10 is effective in promoting allograft survival through blocking Tim-1. However, its role in corneal transplantation is unclear. This study aims to evaluate the effect of RMT1-10 on high-risk corneal transplantation. BALB/c mice were transplanted with corneal grafts from C57BL/6 mice and intraperitoneally injected with RMT1-10 or isotype IgG. The transparency of corneal graft was evaluated by slit lamp biomicroscopy. Flow cytometry was used to determine the phenotype of CD4(+) T cells, including CD154, Tim-3, CD25 and Foxp3, and to analyze the proliferation capacity of CD4(+) T cells and the suppressive capacity of T regulatory (Treg) cells. The levels of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta1 (TGF-beta 1) were investigated by intracellular staining and/or ELISA assay. The delayed-type hypersensitivity (DTH) response was evaluated by ear swelling assay. RMT1-10 therapy delayed the onset of rejection and significantly prolonged the survival of corneal allograft. In RMT1-10 treated mice, percentages of CD4(+)CD154(+) cells and CD4(+)Tim-3(+) cells were significantly decreased while the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells was significantly unregulated, compared with those of isotype IgG treated mice. And, in vitro proliferation of CD4(+) T cells was significantly inhibited by RMT1-10. In addition, percentage of intracellular expression of IFN-gamma and IL-4 in CD4(+) T cells isolated from RMT1-10 treated mice was significantly reduced. After co-culturing with RMT1-10 in vitro, CD4(+) T cells produced significantly decreased levels of IFN-gamma and IL-4 and significantly increased levels of TGF-beta 1. Furthermore, RMT1-10 inhibited DTH response of recipient mice and enhanced the suppressive capacity of Treg cells isolated from RMT1-10 treated mice. Our data indicate that Tim-1 blockade with RMT1-10 could suppress immunological rejection and prolong the survival of corneal allograft through regulating T cell responses. (C) 2014 Elsevier Ltd. All rights reserved.
基金：
Beijing Health Systems High-level Health and Technical Talent Training Plan [2009-2-05]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30801264, 81170824]
第一作者机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalm & Visual Sci Key Lab, Beijing 100730, Peoples R China[2]Chengde Med Coll, Affiliated Hosp, Dept Ophthalmol, Chengde 067000, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalm & Visual Sci Key Lab, Beijing 100730, Peoples R China[*1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China
推荐引用方式(GB/T 7714)：
Tan Xiaobo,Jie Ying,Zhang Yingnan,et al.Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice[J].EXPERIMENTAL EYE RESEARCH.2014,122:86-93.doi:10.1016/j.exer.2014.02.019.
APA：
Tan, Xiaobo,Jie, Ying,Zhang, Yingnan,Qin, Yi,Xu, Qing&Pan, Zhiqiang.(2014).Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice.EXPERIMENTAL EYE RESEARCH,122,
MLA：
Tan, Xiaobo,et al."Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice".EXPERIMENTAL EYE RESEARCH 122.(2014):86-93
