Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers
Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers
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DOI：
10.1182/blood-2004-01-0324
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发表时间：
2004-10-15
期刊：
影响因子：
20.3
通讯作者：
Scheinberg, DA
中科院分区：
文献类型：
--
作者：
Yuan, RR;Wong, P;Scheinberg, DA
目前使用的免疫抑制剂是非特异性的。删除具有独特特异性的特异性CD 8 T细胞克隆的能力可能被证明是剖析CD 8（+）T细胞在人类疾病中的确切作用的有力工具，并且可以形成安全、高选择性治疗自身免疫性疾病的基础。将主要组织相容性复合物（MHC）四聚体（能够结合特异性CD 8 T细胞克隆的多聚体复合物）缀合至Ac-225（α-发射原子纳米发生器，能够从细胞表面进行单击杀伤）以产生用于CD 8 T细胞克隆缺失的试剂。“自杀性”四聚体特异性结合、杀伤和降低其同源CD 8 T细胞（在2个模型系统中的人抗Epstein-巴尔病毒（EBV）或小鼠抗李斯特菌）的功能，同时使非特异性对照CD 8 T细胞群体不受伤害。这种方法可以允许离体或体内选择性消融致病性T细胞克隆而不干扰一般免疫功能的途径。(C)2004年，美国血液学会。
Immunosuppressive agents in current use are nonspecific. The capacity to delete specific CD8T-cell clones of unique specificity could prove to be a powerful tool for dissecting the precise role of CD8(+) T cells in human disease and could form the basis for a safe, highly selective therapy of autoimmune disorders. Major histocompatibility complex (MHC) tetramers (multimeric complexes capable of binding to specific CD8 T-cell clones) were conjugated to Ac-225 (an alpha-emitting atomic nanogenerator, capable of single-hit killing from the cell surface) to create an agent for CD8 T-cell clonal deletion. The "suicide" tetramers specifically bound to, killed, and reduced the function of their cognate CD8 T cells (either human anti-Epstein-Barr virus (EBV) or mouse anti-Listeria in 2 model systems) while leaving the nonspecific control CD8 T-cell populations unharmed. Such an approach may allow a pathway to selective ablation of pathogenic T-cell clones ex vivo or in vivo without disturbing general immune function. (C) 2004 by The American Society of Hematology.