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肿瘤特异性T细胞系:对各种形式的肿瘤抗原作出反应时增殖并产生白细胞介素2的能力。

Tumor-specific T cell lines: capacity to proliferate and produce interleukin 2 in response to various forms of tumor antigens.

作者信息

Shimizu J, Suda T, Katagiri T, Fujiwara H, Hamaoka T

机构信息

Biomedical Research Center, Osaka University Medical School.

出版信息

Jpn J Cancer Res. 1992 Feb;83(2):184-93. doi: 10.1111/j.1349-7006.1992.tb00085.x.

DOI:10.1111/j.1349-7006.1992.tb00085.x
PMID:1372887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5918790/
Abstract

Anti-tumor proliferative T cell lines were established from cultures of lymph node cells from BALB/c mice immunized to syngeneic CSA1M fibrosarcoma with the CSA1M tumor cell membrane. The cultures were maintained throughout in the absence of exogenous interleukin 2 (IL2). Cell surface phenotypes of all T cell lines established were Thy-1+, Ig-, L3T4+ and Lyt-2-. Their proliferation was induced in a tumor antigen dose-dependent fashion and a tumor antigen-specific way. Such proliferative responses were inhibited by the addition to cultures of anti-class II H-2d (anti-I-Ad) or anti-L3T4 but not of anti-class I H-2d or anti-Lyt-2 monoclonal antibody. None of the T cell lines exhibited any cytotoxic T lymphocyte activity but they all produced IL2 upon stimulation with CSA1M tumor antigens, indicating that they represent helper-type T cell (Th) lines. The activation of these tumor-specific Th lines was induced with either CSA1M tumor cells themselves, or their membrane or detergent-solubilized fraction depending on the presence of antigen-presenting cells (APC). Most importantly, activation was also inducible by membranous tumor antigen-pulsed APC, which were capable of producing potent anti-tumor protective immunity when administered in vivo into syngeneic BALB/c mice. These results indicate that the tumor-specific Th lines established here can be activated with various forms of tumor antigens for their expression of helper function. Since Th lines of this type have not been described previously, our Th lines provide an intriguing tool for investigating the cellular and molecular mechanisms by which tumor-specific Th recognize tumor antigens.

摘要

用CSA1M肿瘤细胞膜免疫同基因的BALB/c小鼠,从其淋巴结细胞培养物中建立了抗肿瘤增殖性T细胞系。整个培养过程中均未添加外源性白细胞介素2(IL2)。所建立的所有T细胞系的细胞表面表型均为Thy-1+、Ig-、L3T4+和Lyt-2-。它们的增殖以肿瘤抗原剂量依赖性方式且以肿瘤抗原特异性方式被诱导。将抗II类H-2d(抗I-Ad)或抗L3T4添加到培养物中可抑制这种增殖反应,但添加抗I类H-2d或抗Lyt-2单克隆抗体则无此作用。所有T细胞系均未表现出任何细胞毒性T淋巴细胞活性,但在用CSA1M肿瘤抗原刺激后它们均产生IL2,表明它们代表辅助型T细胞(Th)系。这些肿瘤特异性Th系的激活可由CSA1M肿瘤细胞本身、其细胞膜或去污剂可溶部分诱导,这取决于抗原呈递细胞(APC)的存在。最重要的是,用膜性肿瘤抗原脉冲处理的APC也可诱导激活,当将其体内给予同基因的BALB/c小鼠时,能够产生有效的抗肿瘤保护性免疫。这些结果表明,这里建立的肿瘤特异性Th系可用各种形式的肿瘤抗原激活以表达其辅助功能。由于此前尚未描述过这种类型的Th系,我们的Th系为研究肿瘤特异性Th识别肿瘤抗原的细胞和分子机制提供了一个有趣的工具。

相似文献

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Tumor-specific T cell lines: capacity to proliferate and produce interleukin 2 in response to various forms of tumor antigens.肿瘤特异性T细胞系:对各种形式的肿瘤抗原作出反应时增殖并产生白细胞介素2的能力。
Jpn J Cancer Res. 1992 Feb;83(2):184-93. doi: 10.1111/j.1349-7006.1992.tb00085.x.
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Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts.肿瘤排斥抗原在荷瘤宿主中与抗原呈递细胞发生体内功能性结合的证据。
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Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.用肿瘤抗原脉冲刺激的抗原呈递细胞进行免疫接种诱导肿瘤特异性体内保护性免疫。
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Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.用肿瘤抗原脉冲处理的抗原呈递细胞进行免疫接种诱导肿瘤特异性体内保护性免疫。
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Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.新生期用抗I-A处理的小鼠中Lyt-2-、L3T4+ T细胞系的缺失与胸腺内携带I-A的抗原呈递细胞功能的缺失相关。
J Exp Med. 1985 May 1;161(5):1029-47. doi: 10.1084/jem.161.5.1029.
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Requirements for the generation of a Lyt-2+ T-cell proliferative response to a syngeneic tumor in the absence of L3T4+ T-cells.在缺乏L3T4 + T细胞的情况下,针对同基因肿瘤产生Lyt-2 + T细胞增殖反应的条件。
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Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity.荷瘤小鼠的肿瘤抗原呈递细胞功能逐渐增强,而肿瘤抗原反应性CD4+T细胞活性则相应降低。
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Requirement for recognition of class II molecules and processed tumor antigen for optimal generation of syngeneic tumor-specific class I-restricted CTL.为了最佳地产生同基因肿瘤特异性I类限制性细胞毒性T淋巴细胞(CTL),对II类分子和加工后的肿瘤抗原识别的要求。
J Immunol. 1986 Jun 1;136(11):4303-10.
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The activation of L3T4+ helper T cells assisting the generation of anti-tumor Lyt-2+ cytotoxic T lymphocytes: requirement of Ia-positive antigen-presenting cells for processing and presentation of tumor antigens.辅助抗肿瘤Lyt-2+细胞毒性T淋巴细胞生成的L3T4+辅助性T细胞的激活:Ia阳性抗原呈递细胞处理和呈递肿瘤抗原的必要性。
J Leukoc Biol. 1987 Dec;42(6):632-41. doi: 10.1002/jlb.42.6.632.
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T helper cells in cytotoxic T lymphocyte development: analysis of the cellular basis for deficient T helper cell function in the L3T4-independent T helper cell pathway.细胞毒性T淋巴细胞发育过程中的辅助性T细胞:对L3T4非依赖性辅助性T细胞途径中辅助性T细胞功能缺陷的细胞基础分析。
Cell Immunol. 1991 May;134(2):427-41. doi: 10.1016/0008-8749(91)90315-3.

本文引用的文献

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Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens.分泌针对小鼠H-2和Ia抗原的单克隆抗体的杂交瘤细胞系。
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Monoclonal antibody to L3T4 blocks the function of T cells specific for class 2 major histocompatibility complex antigens.针对L3T4的单克隆抗体可阻断对2类主要组织相容性复合体抗原具有特异性的T细胞的功能。
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Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines.有证据表明L3T4参与II类主要组织相容性复合体(MHC)抗原反应;单克隆抗体GK1.5(抗L3T4a)可阻断II类MHC抗原特异性增殖、淋巴因子释放以及克隆化小鼠辅助性T淋巴细胞系的结合。
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10
Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity.被单克隆抗体GK1.5识别的、命名为L3T4a的鼠类抗原决定簇的特性:功能性T细胞克隆对L3T4a的表达似乎主要与II类主要组织相容性复合体(MHC)抗原反应性相关。
Immunol Rev. 1983;74:29-56. doi: 10.1111/j.1600-065x.1983.tb01083.x.