LAG-3分子的研究进展  

The Research Progress of LAG-3 Molecular

作　　者：何丽[1] 黄长形[1] 李江斌[2] 申焕君[1] 胡萍[1] 朱婷[1] 

机构地区：[1]第四军医大学附属唐都医院传染科,陕西西安710038 [2]第四军医大学附属唐都医院普通外科,陕西西安710038

出　　处：《现代生物医学进展》2014年第15期2989-2993,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81072434)

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。Lymphocyte activation gene -3 （lymphocyte activation gene-3, LAG-3, CD223） is one ofimmunoglobulin 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 Trl cell.CD49b and LAG-3 is found, which make purified Trl 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 surro- gate 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 expres- sion 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 MHC Ⅱ, 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-MHC Ⅱ 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 de- layed-type hypersensitivity.

关 键 词：LAG-3 TR细胞 糖尿病 肿瘤 病毒感染 

分 类 号：R392.1[医药卫生—免疫学]