Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, Mexico City, Mexico.
Autoimmun Rev. 2013 Oct;12(12):1171-6. doi: 10.1016/j.autrev.2013.07.002. Epub 2013 Jul 11.
Cytotoxic T-Lymphocye Antigen 4 (CTLA-4) or CD152 is an inhibitory molecule that plays a critical role in maintenance of tolerance to self-antigens. CTLA-4 is structurally as well as functionally related to CD28, since it shares 31% of homology and binds the B7 family molecules CD80 and CD86 with higher affinity. Nevertheless, CTLA-4 has opposing effects on T cell activation and current evidence shows that its inhibitory role goes beyond the ligand-binding interaction. CTLA-4 competes with CD28 in binding to B7, interacts within the immunological synapsis elements and with clathrin adaptor proteins and tyrosine phosphatases through its cytoplasmic domain to regulate cell trafficking and to set the activation threshold within T cells. Moreover, we have learned from the knock out model that CTLA-4 plays a key role in regulatory T cells and in central tolerance. Because of its importance in maintenance of peripheral tolerance, CTLA-4 has been implicated in several autoimmune diseases, such as systemic lupus erythematosus. Multiple single-nucleotide polymorphisms have been located to human Ctla-4 gene, and their association with autoimmune disease is still a matter of controversy. Despite the promising results of abatacept or CTLA-4-Ig in rheumatoid arthritis and murine lupus nephritis, more clinical randomized trials and standardization of outcomes are needed to prove its efficacy and safety in human lupus nephritis.
细胞毒性 T 淋巴细胞抗原 4（CTLA-4）或 CD152 是一种抑制性分子，在维持对自身抗原的耐受性方面起着关键作用。CTLA-4 在结构和功能上与 CD28 相关，因为它共享 31%的同源性，并以更高的亲和力结合 B7 家族分子 CD80 和 CD86。然而，CTLA-4 对 T 细胞活化有相反的影响，目前的证据表明其抑制作用超出了配体结合相互作用。CTLA-4 与 CD28 竞争与 B7 的结合，在免疫突触元件内相互作用，并通过其细胞质结构域与网格蛋白衔接蛋白和酪氨酸磷酸酶相互作用，从而调节细胞迁移并在 T 细胞内设定激活阈值。此外，我们从敲除模型中了解到，CTLA-4 在调节性 T 细胞和中枢耐受中发挥关键作用。由于其在维持外周耐受中的重要性，CTLA-4 已被涉及到几种自身免疫性疾病，如系统性红斑狼疮。已经在人类 Ctla-4 基因中定位了多个单核苷酸多态性，其与自身免疫性疾病的关联仍然存在争议。尽管阿巴西普或 CTLA-4-Ig 在类风湿关节炎和小鼠狼疮肾炎中的疗效令人鼓舞，但仍需要更多的临床随机试验和结果标准化来证明其在人类狼疮肾炎中的疗效和安全性。
