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体外免疫核糖核酸加速同种异体抗肿瘤免疫及L1210荷瘤小鼠脾细胞对T细胞的抑制作用

Acceleration of allogeneic antitumor immunity with immune RNA in vitro and T-cell suppression by L1210 tumor bearer spleen cells.

作者信息

Miura T, Maekawa T, Kurashige S, Mitsuhashi S

出版信息

Cancer Res. 1981 Feb;41(2):383-98.

PMID:6160907
Abstract

RNA fractions extracted from the spleens of immunized animals prepared against L1210 leukemia cells can transfer allospecific cell-mediated immunity both in vitro and in vivo. Both preculture of nonsensitized lymphocytes prior to the treatment with immune RNA and additional culture of lymphocytes after 1-hr treatment with immune RNA enhance the growth-inhibitory activity of immune RNA-treated lymphocytes. Preculture for 5 hr and additional culture for 24 hr are sufficient for maximal enhancement of the growth-inhibitory activity. There is no significant difference in inhibition between lymphocytes treated with immune RNA for 1 hr and 24 hr. The growth inhibition by lymphocytes is augmented proportionally to the increase in the dose of immune RNA in vitro but not in vivo. In mice given i.p. injections of immune RNA-treated syngeneic spleen cells (before or after inoculation with L1210 cells), a significant prolongation of the mean survival time [27.0 +/- 5.4 (S.D.) days, 0.05 < p < 0.1] was not achieved when compared with control mice (21.4 +/- 1.6 days). Evidence is presented that suppressor cells in the spleens of L1210-bearing mice are involved in preventing effector cell function in vivo. The present study revealed that 8 X 10(3) and 5 X 10(5) suppressor cells were sufficient to inhibit completely the activity of immune RNA-treated effector cells in vitro and in vivo, respectively. Suppressive activity was abolished by treatment with anti-Thy 1.2 serum and complement and partially abolished with irradiation (1500 R). The suppressor cells belonged to a radiation-sensitive T-cell population. The limited activity of immune RNA in vivo is probably due to the destruction of immune RNA by RNase present in the host plasma and tissues and the acquisition of suppressor cells which inhibits nonadherent peritoneal exudate cell activity in the animal.

摘要

从针对L1210白血病细胞制备的免疫动物脾脏中提取的RNA组分,在体外和体内均可传递同种特异性细胞介导的免疫。在用免疫RNA处理之前对未致敏淋巴细胞进行预培养,以及在用免疫RNA处理1小时后对淋巴细胞进行额外培养,均可增强免疫RNA处理的淋巴细胞的生长抑制活性。预培养5小时和额外培养24小时足以最大程度地增强生长抑制活性。用免疫RNA处理1小时和24小时的淋巴细胞之间的抑制作用无显著差异。淋巴细胞的生长抑制在体外与免疫RNA剂量的增加成比例增强,但在体内并非如此。在腹腔注射免疫RNA处理的同基因脾细胞的小鼠中(在接种L1210细胞之前或之后),与对照小鼠(21.4±1.6天)相比,平均存活时间并未显著延长[27.0±5.4(标准差)天,0.05<p<0.1]。有证据表明,携带L1210的小鼠脾脏中的抑制细胞参与了体内效应细胞功能的抑制。本研究表明,分别有8×10³和5×10⁵个抑制细胞足以在体外和体内完全抑制免疫RNA处理的效应细胞的活性。用抗Thy 1.2血清和补体处理可消除抑制活性,而照射(1500 R)可部分消除抑制活性。抑制细胞属于对辐射敏感的T细胞群体。免疫RNA在体内的活性有限,可能是由于宿主血浆和组织中存在的核糖核酸酶对免疫RNA的破坏,以及获得了抑制动物中非粘附性腹腔渗出细胞活性的抑制细胞。

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