RNA MODULATING SPECIFIC AND NONSPECIFIC IMMUNE RESPONSES

RNA MODULATING SPECIFIC AND NONSPECIFIC IMMUNE RESPONSES
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RNA 调节特异性和非特异性免疫反应

DOI:
10.1111/j.1749-6632.1979.tb47112.x
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发表时间:
1979
影响因子:
5.2
通讯作者:
H. Friedman
H. Friedman
中科院分区:
综合性期刊3区
文献类型:
--
作者:
H. Friedman

文献摘要

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对抗原的免疫应答涉及几种不同细胞类型之间的一系列复杂的相互作用。至少有三种不同的细胞可能参与对颗粒抗原的体液和细胞免疫应答;这些细胞包括产生抗体的B淋巴细胞、调节性T淋巴细胞和抗原"加工"巨噬细胞,它们似乎具有中介作用,但不是抗原特异性作用。在这方面,自从第一个实验报道来自免疫动物的淋巴组织以及来自巨噬细胞的亚细胞提取物在体内或体外可以将免疫应答转移到非免疫受体动物或体外培养的淋巴细胞悬液以来,已经过去了近20年。存在于这些提取物中的富含RNA的部分已经被暗示为这种转移反应中的活性因子。已发现RNA本身或RNA-抗原复合物参与形成针对多种抗原的抗体,以及参与细胞介导的免疫,如体外和体内同种异体应答或抗肿瘤免疫反应。4 - 8本实验室过去20年的研究表明,来自脾、用细菌抗原免疫的兔或小鼠的淋巴结或腹膜细胞,以及绵羊红细胞,在正常或X射线照射受体同系动物中诱导特异性免疫应答1.9 - 15类似RNA-来自免疫供体动物的丰富提取物在体外诱导特异性抗体形成,如在细胞水平上通过多种抗体测定所测量的。抗体应答对用于免疫供体动物或细胞悬液的抗原具有特异性。在本实验室的许多早期实验中,富含高免疫原性脂多糖的志贺氏菌提取物被用作免疫原,用于兔或随后,许多研究用绵羊红细胞作为抗原,并在琼脂凝胶中进行局部溶血空斑试验以检测抗体应答。z-15当供体细胞悬浮液针对抗原特异性免疫时,受体应答与供体以及受体的抗原刺激有关,即,已经对抗原致敏的小鼠的脾细胞在暴露于来自初次注射相同而不是不同抗原的小鼠的富含RNA的提取物时显示出二次应答。此外,注意到富含RNA的提取物诱导受体中的抗体形成,即使供体动物对抗原特异性耐受,即,当给予RNA-抗原提取物时,供体动物不能以可检测的方式对抗原作出反应,但受体细胞却可以。RNA酶和抗原的抗血清都阻断了转移反应,支持了活性RNA-抗原复合物参与反应的观点。然而,在所有这些研究中,正常脾细胞悬浮液在没有抗原但与来自正常供体的RNA提取物一起孵育时,
Immune responses to antigens involve a complex series of interactions among several distinct cell types. At least three different cells may be involved in both humoral and cellular immune responses to particulate antigens; these include antibody-producing B-lymphocytes, regulatory T-lymphocytes and antigen-"processing" macrophages, which appear to have an intermediary but not antigen-specific role. In this regard, it has been nearly two decades since the first experiments were reported indicating that subcellular extracts derived from lymphoid tissues of immunized animals, as well as from macrophages, either in vivo or in vitro, may transfer immune responsiveness to nonimmune recipient animals or lymphoid cell suspensions cultured in ~ i t r o . l ~ RNA-rich moieties present in these extracts have been implicated as the active factor in such transfer reactions. RNA per se, or an RNA-antigen complex have been found to be involved in formation of antibody to a wide variety of antigens, as well as in cell-mediated immunity, such as allogeneic responses in vitro and in vivo or in antitumor immune reactions.4-8 Studies in this laboratory over the past 20 years have shown that RNA-rich extracts from the spleen, lymph nodes or peritoneal cells of rabbits or mice immunized with bacterial antigens, as well as sheep erythrocytes, induce specific immune responses in either normal or x-irradiated recipient syngeneic anima1.9-15 Similar RNA-rich extracts from immunized donor animals induced specific antibody formation in vitro as measured by a variety of antibody assays at the cell level. Antibody responses were specific to the antigen utilized for immunizing the donor animals or cell suspensions. In many of the early experiments in this laboratory, Shigella extracts rich in the highly immunogenic lipopolysaccharides were used as the immunogen, either for rabbits or Subsequently, many studies were performed with sheep erythrocytes as the antigen and the localized hemolytic plaque assay in agar gel for detecting the antibody responses.*z-15 When donor cell suspensions were specifically immunized to an antigen, the recipient response was related to the antigenic stimulus of the donor as well as the recipient, i.e., spleen cells of mice already primed to an antigen showed a secondary response upon exposure to RNA-rich extracts from mice given a primary injection of the same, but not a different antigen. Furthermore, it was noted that RNA-rich extracts induced antibody formation in recipients even when the donor animals were specifically tolerant to the antigen, i.e., the donor animals could not respond in a detectable manner to the antigen but recipient cells did so when given the RNA-antigen extracts. Both RNase and antisera to the antigen blocked the transfer reaction, supporting the view that an active RNA-antigen complex was involved in the reactions.ll. l 5 In all of these studies, however, normal spleen cell suspensions, when incubated without antigen but with the RNA extracts from normal donors,