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长寿细胞毒性T细胞克隆对同基因淋巴瘤的保护作用。

Protection against syngeneic lymphoma by a long-lived cytotoxic T-cell clone.

作者信息

Dailey M O, Pillemer E, Weissman I L

出版信息

Proc Natl Acad Sci U S A. 1982 Sep;79(17):5384-7. doi: 10.1073/pnas.79.17.5384.

Abstract

The effect of a cloned T-cell line on the in vivo growth of syngeneic lymphoma cells was studied. 1E4 is an H-2-restricted cytotoxic T-cell clone that efficiently kills Abelson virus-induced lymphoma target cells (L1-2) at low effector/target ratios, as measured by in vitro cytotoxicity assays. In addition, it is long lived in vitro in the absence of stimulation and survives for more than 1 wk in vivo in the absence of exogenous antigen or growth factors. Mice injected intraperitoneally with lethal doses of L1-2 and then treated with 1E4 survived longer than animals treated with saline or with a control T-cell clone. Multiple weekly injections of effector cells, or a single injection in animals given a low dose of tumor cells, resulted in 50-80% long-term survivors. The observation that intravenous injection of killer cells was less effective than intraperitoneal treatment, coupled with the previous demonstration of markedly abnormal circulatory patterns for T-cell clones, suggests that those animals succumbing to progressively growing neoplasm die because the effector cells are unable to home into peripheral sites of tumor deposition. Thus, although this cytotoxic T-cell clone does have useful in vivo activity, its function may be partially limited by a generalized defect in migration.

摘要

研究了克隆的T细胞系对同基因淋巴瘤细胞体内生长的影响。1E4是一个H-2限制性细胞毒性T细胞克隆,通过体外细胞毒性试验测定,它能在低效应细胞/靶细胞比例下有效杀伤艾贝尔森病毒诱导的淋巴瘤靶细胞(L1-2)。此外,在无刺激条件下它在体外存活时间长,在无外源性抗原或生长因子的情况下在体内能存活超过1周。腹腔注射致死剂量L1-2后再用1E4治疗的小鼠比用生理盐水或对照T细胞克隆治疗的动物存活时间更长。每周多次注射效应细胞,或对给予低剂量肿瘤细胞的动物单次注射,可产生50%-80%的长期存活者。静脉注射杀伤细胞不如腹腔治疗有效的观察结果,再加上先前证明T细胞克隆的循环模式明显异常,表明那些死于肿瘤进行性生长的动物是因为效应细胞无法归巢到肿瘤沉积的外周部位。因此,尽管这种细胞毒性T细胞克隆确实具有有用的体内活性,但其功能可能部分受到迁移普遍缺陷的限制。

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