LONG-TERM SURVIVAL OF XENOGENEIC PANCREATIC-ISLET GRAFTS INDUCED BY CTLA4IG
LONG-TERM SURVIVAL OF XENOGENEIC PANCREATIC-ISLET GRAFTS INDUCED BY CTLA4IG
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DOI：
10.1126/science.1323143
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发表时间：
1992-08-07
期刊：
影响因子：
56.9
通讯作者：
BLUESTONE, JA
中科院分区：
文献类型：
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作者：
LENSCHOW, DJ;ZENG, YJ;BLUESTONE, JA
抗原特异性T细胞的激活依赖于T细胞受体-配体的相互作用和辅助分子与其配体结合时产生的共刺激信号，如CD28与B7(也称为BB1)分子的结合。人CTLA-4(一种与CD28同源的蛋白)与免疫球蛋白(Ig)G1 Fc区(CTLA4Ig)的可溶性融合蛋白(CTLA4Ig)可高亲和力地与人和小鼠B7结合，体外阻断T细胞的激活。CTLA4Ig治疗通过直接影响T细胞对B7+抗原提呈细胞的识别来阻断小鼠的人胰岛排斥反应。此外，CTLA4Ig诱导了长期的供体特异性耐受，这可能会应用于人类器官移植。
Antigen-specific T cell activation depends on T cell receptor-ligand interaction and co-stimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (Ig) G1 Fc region (CTLA4Ig) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4Ig therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells. In addition, CTLA4Ig induced long-term, donor-specific tolerance, which may have applications to human organic transplantation.