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通过将抗T3与抗靶细胞抗体交联形成的异聚体对人外周血T细胞进行特异性靶向。

Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies.

作者信息

Perez P, Hoffman R W, Titus J A, Segal D M

出版信息

J Exp Med. 1986 Jan 1;163(1):166-78. doi: 10.1084/jem.163.1.166.

Abstract

Antibody heteroaggregates have been used to render human peripheral blood T cells lytic for specified targets. The heteroaggregates contain anti-T3 covalently linked to antibodies against nominal target cell antigens. Such heteroaggregates bind target cells directly to T3 molecules on effector cells and trigger target cell lysis. Freshly prepared human PBL, when coated with anti-T3-containing heteroaggregates, are lytic without further stimulation, although brief exposure to crude lymphokine-containing supernatants or recombinant IL-2, but not recombinant IFN-gamma, enhances the activity. The effector cells are T8+, and when fully stimulated, their lytic activity approaches that of some cloned CTL. When T cells are treated with heteroaggregate, washed, and incubated at 37 degrees C in medium not containing heteroaggregate, they retain activity for at least 24 h. The results of this study suggest a strategy in which heteroaggregate-coated T cells could be used in vivo to mount a lytic response against pathogenic cells such as tumor cells or virus-infected cells.

摘要

抗体异聚体已被用于使人类外周血T细胞对特定靶标具有细胞溶解活性。这些异聚体包含与针对名义靶细胞抗原的抗体共价连接的抗T3。此类异聚体将靶细胞直接与效应细胞上的T3分子结合,并触发靶细胞裂解。新鲜制备的人外周血淋巴细胞(PBL),当用含抗T3的异聚体包被时,无需进一步刺激即可具有细胞溶解活性,尽管短暂暴露于含粗制淋巴因子的上清液或重组白细胞介素-2(IL-2)而非重组干扰素-γ(IFN-γ)可增强其活性。效应细胞为T8 +,当被充分刺激时,其细胞溶解活性接近某些克隆的细胞毒性T淋巴细胞(CTL)。当T细胞用异聚体处理、洗涤并在不含异聚体的培养基中于37℃孵育时,它们至少可保持活性24小时。本研究结果提示了一种策略,即包被有异聚体的T细胞可在体内用于对诸如肿瘤细胞或病毒感染细胞等致病细胞发起细胞溶解反应。

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