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何丽1 黄长形1△ 李江斌2 申焕君1 胡萍1 朱婷1.LAG-3 分子的研究进展*[J].现代生物医学进展英文版,2014,14(15):2989-2993.
LAG-3 分子的研究进展*
The Research Progress of LAG-3 Molecular*
  
DOI:
中文关键词: LAG-3  Tr细胞  糖尿病  肿瘤  病毒感染
英文关键词: LAG-3  Tr cell  Diabetes  Tumor  Virus infection
基金项目:国家自然科学基金项目(81072434)
Author NameAffiliation
HE Li, HUANG Chang-xing, LI Jiang-bin,SHEN Huan-jun, HU Ping, ZHU Ting 1 第四军医大学附属唐都医院传染科陕西西安7100382 第四军医大学附属唐都医院普通外科陕西西安710038 
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中文摘要:
      摘要:淋巴细胞活化基因-3(lymphocyte activation gene-3,LAG-3,CD223)是免疫球蛋白超家族的成员之一,是对淋巴细胞具有抑 制作用的分子。LAG-3定位于人12 号染色体,与CD4 具有密切关系。研究发现猪LAG-3 分子的结构和表达模式在哺乳动物物种 中是共有的,并且可溶性的猪LAG-3 对控制人-猪异种T 细胞免疫反应有作用。LAG-3 分子主要表达于活化的NK 细胞、T 淋巴 细胞表面,与HLA-II高亲和力结合。Tr 细胞是具有调节调节功能的T 细胞亚群,发现Tr 细胞表面标志CD49b 和LAG-3可在人 和小鼠Tr1 细胞表面表达。CD49b 和LAG-3 的发现,使得在体内对Tr细胞进行跟踪具有可行性,纯化Tr1 细胞作为一种细胞治 疗方法具有可行性。LAG-3通过对胰腺中抗原特异性T 细胞增殖的选择性抑制,可以使用LAG-3 作为1型糖尿病病情进展的一 种新的替代标记,检测LAG-3 分子可能成为T细胞定向免疫治疗效果评估的一种方法。肿瘤浸润的CD8+T细胞表面LAG-3 表 达上调,LAG-3 的抑制作用在HCC的细胞免疫应答中发挥着重要的作用,可见阻断LAG-3 分子的表达有可能成为治疗肿瘤的 新方法。慢性病毒感染性疾病时常常发生T 细胞衰竭,T细胞通过LAG-3 分子的限制作用和MHCⅡ类信号分子的表达其抑制功 能,这有利于慢性病毒感染性疾病的治疗。疟原虫感染增加了抑制性受体LAG-3 的表达,疟原虫感染引起的特异性T细胞功能 衰竭可通过抑制性疗法来治疗。LAG-3 的表达可能有利于黑色素瘤的增殖,阻断LAG-3-MHCⅡ类分子相互作用的化合物可用于 黑色素瘤的治疗。此外,使用LAG-3 毒性抗体选择性的靶向激活T 细胞可阻碍T 细胞参与的迟发型超敏反应。
英文摘要:
      ABSTRACT:Lymphocyte activation gene -3 (lymphocyte activation gene-3, LAG-3, CD223) is one of immunoglobulin superfamily numbers. It is a inhibitory molecule for lymphocytes. LAG-3 is located on human chromosome 12, a close relationship with CD4.Study found that pig LAG-3 molecule structure and expression patterns in mammalian species are common. Soluble pig LAG-3 play a role in person - Pig heterologous T cell immune responses. LAG-3 molecule is mainly expressed on activated NK cells, T lymphoctes. It has high affinity with HLA-II. Tr cells are capable of regulating the regulatory function of T cell subsets and found Tr cell surface markers CD49b and LAG-3 in human and mouse Tr1 cell.CD49b and LAG-3 is found, which make purified Tr1 cells as a cell therapy approach become feasible LAG-3 could inhibit selectively antigen-specific T cells in the pancreas. As a result, LAG-3 can be used as a new surrogate marker in the progression of type 1 diabetes. Detecting LAG-3 molecules may be a new method in directed T cell immunotherapy effect assessment. Tumor infiltrating CD8+ T cells up-regulated LAG-3. LAG-3 plays an important role in HCC. Blocking the expression of LAG-3 molecule may become a new method of cancer treatment. Chronic viral infection often occurs when T cells failure. T cells play its suppression function via the limitations of LAG-3 molecule and MHCⅡ, which is conducive to chronic viral infectious diseases. Plasmodium infection increases the expression of LAG-3, and it could be treated by inhibiting therapy. LAG-3 expression may favor the proliferation of melanoma, and blocking LAG-3-MHCⅡ molecules interacting compounds can be used in the treatment of melanoma. In addition, the use of LAG-3 antibodies selective toxicity of T cell activation can hinder targeting T cells which were involved in delayed- type hypersensitivity.
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