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Tumor immune escape by immunoregulatory CD4 T cells

免疫调节 CD4 T 细胞的肿瘤免疫逃逸

基本信息

批准号：
10670304
负责人：
NAKAYAMA Eiichi
金额：
$ 1.79万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670304/
关键词：
murine tumor tumor rejection antigen immune surveillance tumor immune escape immune regulation regulatory CD4 T cells regulatory CD4ィイD1+ィエD1CD25ィイD1+ィエD1 T cells 腫瘍免疫マウス白血病腫瘍エスケープ CD25 モノクロナール抗体

项目摘要

Cancer immune surveillance theory has been widely accepted, but the scientific basis is still obscure. Tumor immune escape is also a theory of which mechanisms have not fully elucidated. Recently, tumor antigens recognized by the host immune system have been identified at molecular level, and the analysis of tumor immune responses against the tumor immunology, theories of the immune surveillance and the tumor immune escape should be carefully reevaluated.In this study, using BALB/c radiation leukemia RL♂1 on which we previously identified the antigen peptide recognized by the specific CTL as a model tumor, we identified tumor antigen specific regulatory CD4 T cells. We showed that altered Akt molecule which is dominant antigen in RL♂1 stimulated immunoregulatory CD4 T cells and inhibited efficient generation of CD8 CTL which recognized the tumor antigen peptide derived also from the Akt molecule.Beside those tumor antigen specific regulatory CD4 T cells, we also found immunoregulatory CD4ィイD1+ィエD1CD25ィイD1+ィエD1 T cells which were tumor antigen non-specific. Those cells were activated by autoantigens and protected from auto immunity. We showed that by in vivo depletion of CD4ィイD1+ィエD1CD25ィイD1+ィエD1 T cells, efficient tumor rejection response occurred.

肿瘤免疫监测理论已被广泛接受，但其科学依据尚不清楚。肿瘤免疫逃逸也是一种机制尚未完全阐明的理论。近年来，宿主免疫系统识别的肿瘤抗原已经在分子水平上得到了鉴定，肿瘤免疫应答的分析、免疫监视和肿瘤免疫逃逸的理论都需要重新审视。本研究以BALB/c放射性白血病RL-♂1为模型肿瘤，我们鉴定了肿瘤抗原特异性的调节性T细胞。我们发现，RL♂1的优势抗原AKT分子的改变刺激了免疫调节性CD4T细胞，抑制了CD8CTL的高效产生，CD8CTL识别肿瘤抗原肽，除了肿瘤抗原特异性调节性CD4T细胞外，我们还发现了肿瘤抗原非特异性的免疫调节性CD4CDD1+ィイD1CD25ィエD1CD25ィイD1+ィエD1T细胞。这些细胞被自身抗原激活，不受自身免疫的影响。我们发现，通过体内去除CD_4ィイD_1+ィエD_1CD_(25)ィイD_1+ィエD_1T细胞，发生了有效的肿瘤排斥反应。