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用荷瘤小鼠脾脏RNA处理的正常淋巴细胞释放可溶性“封闭”因子和“抑制”因子。

Release of soluble "blocking" and "suppressor" factors from normal lymphocytes treated with RNA from spleens of tumour-bearing mice.

作者信息

Pennline K J, Evans S B, Nawrocki J F, Rees J C, Johnson C S, Vallera D A, Dodd M C

出版信息

Br J Cancer. 1979 Mar;39(3):247-58. doi: 10.1038/bjc.1979.48.

Abstract

RNA extracted from the spleens of tumour-bearing (TLRNA) and tumour-immune (ILRNA) mice was shown to transfer to normal lymphocytes (NL) the ability to produce factors that blocked specific tumour-cell cytotoxicity and mediated specific antibody-dependent cell cytotoxicity (ADCC). Aliquots of normal C3H mouse lymphocytes were treated with TLRNA or ILRNA and cultured in vitro in the absence of tumour antigen. Supernatants were collected at 24h intervals and tested in a microcytotoxicity assay for blocking and ADCC activities. Factors that inhibited tumour destruction by specifically sensitized lymphocytes at the level of both the tumour cells and effector cells were demonstrable in culture supernatants of NL pretreated with TLRNA (50 or 100 microgram/4 X 10(6) cells) but not ILRNA. However, treatment of NL with either RNA resulted in the production factors that mediated tumour-specific ADCC. Cytotoxicity testing and absorption studies of the tumour cell and a control cell (LM) indicated that factors mediating ADCC and blocking at the target-cell level were specific for the tumour. Suppressor activity at the effector-cell level was not absorbed by tumour cells and represents a separate and distinct mechanism of immunosuppression. These data indicate that RNA faithfully transfers "suppressive" as well as "positive" types of immune responses that have been reported previously for lymphocytes obtained directly from tumour-bearing and tumour-immune animals.

摘要

从荷瘤小鼠(TLRNA)和肿瘤免疫小鼠(ILRNA)脾脏中提取的RNA被证明能将产生阻断特异性肿瘤细胞细胞毒性并介导特异性抗体依赖性细胞毒性(ADCC)因子的能力转移至正常淋巴细胞(NL)。取正常C3H小鼠淋巴细胞的等分试样,用TLRNA或ILRNA处理,并在无肿瘤抗原的情况下进行体外培养。每隔24小时收集上清液,并在微量细胞毒性试验中检测其阻断和ADCC活性。在用TLRNA(50或100微克/4×10⁶个细胞)预处理的NL培养上清液中可检测到在肿瘤细胞和效应细胞水平均能抑制特异性致敏淋巴细胞对肿瘤破坏的因子,而在用ILRNA预处理的培养上清液中则检测不到。然而,用任一种RNA处理NL均会产生介导肿瘤特异性ADCC的因子。对肿瘤细胞和对照细胞(LM)进行的细胞毒性测试及吸收研究表明,在靶细胞水平介导ADCC和阻断作用的因子对肿瘤具有特异性。效应细胞水平的抑制活性不会被肿瘤细胞吸收,代表一种独立且不同的免疫抑制机制。这些数据表明,RNA如实地转移了先前报道的直接从荷瘤动物和肿瘤免疫动物获得的淋巴细胞所具有的“抑制性”以及“阳性”免疫反应类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf54/2009868/bfcf624c4660/brjcancer00149-0037-a.jpg

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