Shimizu J, Suda T, Katagiri T, Fujiwara H, Hamaoka T
Biomedical Research Center, Osaka University Medical School.
Jpn J Cancer Res. 1992 Feb;83(2):184-93. doi: 10.1111/j.1349-7006.1992.tb00085.x.
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.
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。