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Type 1 diabetes induction in humanized mice 期刊论文

编号：

4865e77a-ec82-4c38-a28b-5b53c0208718
作者：

Tan, Shulian(谭淑莲)#^[1,2,3,4]Li, Yang^[1,2,3,4];Xia, Jinxing^[4];Jin, ChunHui^[1,4];Hu, Zheng(胡正)^[1,2,3]Duinkerken, Gaby^[5];Li, Yuying(李昱瑛)^[1,4]Maharlooei, Mohsen Khosravi^[4];Chavez, Estefania^[4];Nauman, Grace^[4];Danzl, Nichole^[4];Nakayama, Maki^[6];Roep, Bart O.^[5,7];Sykes, Megan^[4];Yang, YongGuang(杨永广)*^[1,2,3,4]
语种：

英文
期刊：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ISSN：0027-8424 2017 年 114 卷 41 期 (10954 - 10959) ; OCT 10
收录：
关键词：

type 1 diabetes insulin humanized mice
摘要：

There is an urgent and unmet need for humanized in vivo models of type 1 diabetes to study immunopathogenesis and immunotherapy, and in particular antigen-specific therapy. Transfer of patient blood lymphocytes to immunodeficient mice is associated with xenogeneic graft-versus-host reactivity that complicates assessment of autoimmunity. Improved models could identify which human T cells initiate and participate in beta-cell destruction and help define critical target islet autoantigens. We used humanized mice (hu-mice) containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity to address this question. Hu-mice constructed by transplantation of HLA-DQ8(+) human fetal thymus and CD34(+) cells into HLA-DQ8-transgenic immunodeficient mice developed hyperglycemia and diabetes after transfer of autologous HLA-DQ8/insulin-B:9-23 (InsB:9-23)-specific T-cell receptor (TCR)-expressing human CD4(+) T cells and immunization with InsB:9-23. Survival of the infused human T cells depended on the preexisting autologous human immune system, and pancreatic infiltration by human CD3(+) T cells and insulitis were observed in the diabetic hu-mice, provided their islets were stressed by streptozotocin. This study fits Koch"s postulate for pathogenicity, demonstrating a pathogenic role of islet autoreactive CD4(+) T-cell responses in type 1 diabetes induction in humans, underscores the role of the target beta-cells in their immunological fate, and demonstrates the capacity to initiate disease with T cells, recognizing the InsB:9-23 epitope in the presence of islet inflammation. This preclinical model has the potential to be used in studies of the pathogenesis of type 1 diabetes and for testing of clinically relevant therapeutic interventions.
推荐引用方式
GB/T 7714：

Tan Shulian,Li Yang,Xia Jinxing, et al. Type 1 diabetes induction in humanized mice [J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017,114(41):10954-10959.
APA：

Tan Shulian,Li Yang,Xia Jinxing,Jin Chun-Hui,&Yang Yong-Guang.(2017).Type 1 diabetes induction in humanized mice .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,114(41):10954-10959.
MLA：

Tan Shulian, et al. "Type 1 diabetes induction in humanized mice" .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114,41(2017):10954-10959.
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