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

作者: Shang Li , Hongshuang Lu , Ruti Sella , Wei Zhang , Hongwei Dong

DOI: 10.1038/S41598-018-26235-5

关键词:

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

参考文章(36)
K. Cunnusamy, J. Y. Niederkorn, IFN-γ blocks CD4+CD25+ Tregs and abolishes immune privilege of minor histocompatibility mismatched corneal allografts. American Journal of Transplantation. ,vol. 13, pp. 3076- 3084 ,(2013) , 10.1111/AJT.12466
Xiaoqi Zhao, Yuzhou Liu, Yucheng Zhong, Bo Liu, Kunwu Yu, Huairui Shi, Ruirui Zhu, Kai Meng, Wei Zhang, Bangwei Wu, Qiutang Zeng, Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP Mediators of Inflammation. ,vol. 2015, pp. 841472- 841472 ,(2015) , 10.1155/2015/841472
Xiao-Tang Yin, Stephanie Zobell, Jason G. Jarosz, Patrick M. Stuart, Anti–IL-17 Therapy Restricts and Reverses Late-Term Corneal Allorejection Journal of Immunology. ,vol. 194, pp. 4029- 4038 ,(2015) , 10.4049/JIMMUNOL.1401922
Eyad Elkord, May Abd Al Samid, Belal Chaudhary, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP Oncotarget. ,vol. 6, pp. 20026- 20036 ,(2015) , 10.18632/ONCOTARGET.4771
Maria-Grazia Roncarolo, Silvia Gregori, Is FOXP3 a bona fide marker for human regulatory T cells European Journal of Immunology. ,vol. 38, pp. 925- 927 ,(2008) , 10.1002/EJI.200838168
Shohei Hori, Takashi Nomura, Shimon Sakaguchi, Control of Regulatory T Cell Development by the Transcription Factor Foxp3 Science. ,vol. 299, pp. 1057- 1061 ,(2003) , 10.1126/SCIENCE.1079490
Haiyan Wei, Kehong Tan, Rongli Sun, Lihong Yin, Juan Zhang, Yuepu Pu, Aberrant Production of Th1/Th2/Th17-Related Cytokines in Serum of C57BL/6 Mice after Short-Term Formaldehyde Exposure International Journal of Environmental Research and Public Health. ,vol. 11, pp. 10036- 10050 ,(2014) , 10.3390/IJERPH111010036
Keryn A. Williams, Adrian J. Esterman, Christine Bartlett, Helene Holland, Ngaere B. Hornsby, Douglas J. Coster, How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis. Transplantation. ,vol. 81, pp. 896- 901 ,(2006) , 10.1097/01.TP.0000185197.37824.35
Naoto Sasaki, Tomoya Yamashita, Masafumi Takeda, Masakazu Shinohara, Kenji Nakajima, Hideto Tawa, Takashi Usui, Ken-ichi Hirata, Oral Anti-CD3 Antibody Treatment Induces Regulatory T Cells and Inhibits the Development of Atherosclerosis in Mice Circulation. ,vol. 120, pp. 1996- 2005 ,(2009) , 10.1161/CIRCULATIONAHA.109.863431
BING LI, LIHUA TIAN, YUMEI DIAO, XUE LI, LIYING ZHAO, XUEFENG WANG, Exogenous IL-10 induces corneal transplantation immune tolerance by a mechanism associated with the altered Th1/Th2 cytokine ratio and the increased expression of TGF-β Molecular Medicine Reports. ,vol. 9, pp. 2245- 2250 ,(2014) , 10.3892/MMR.2014.2073