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The similarity between pregnant immunity and tumor immunity

妊娠免疫与肿瘤免疫的相似性

基本信息

批准号：
17390447
负责人：
SAITO Shigeru
金额：
$ 10.41万
依托单位：
University of Toyama
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390447/
关键词：
pregnancy tumor immunology IDO regulatory T cell regulatory NK cell tolerance 制御性NK細胞 ID0 妊娠癌免疫トレランス NK細胞

项目摘要

Fetus is a semiallograft to maternal host, therefore immune-tolerance system should be present during pregnancy. Inadequate tolerance induction might induce miscarriage or pregnancy induced hypertension (PIH). Tumor cells also escape the immunological attack, therefore there are many similarity between pregnancy immunity and tumor immunity. From the view point of pregnancy immunity, we found that C1D4^+ CD25^+ regulatory T (Treg) cells are increased at materno - fetal interface, and these cells are decreased in miscarriage and PIH cases. We also clarified that indoleamine 2,3-dioxygenase (IDO) expressing dendritic cells (DC) and macrophage play very important roles for maintenance of pregnancy. In cervical cancer, IDO expression in tumor cells, appeared in cervical intraepithelial neoplasia (CIN) - 3 of the uterine cervix and marked expression in microinvasive cancer cells was observed. Interestingly, IDO expression was confined to the cancer cells at the invasive front. Moreover antigen - presenting cell at the invasive front in primary and metastatic lesions were also expressing IDO. Treg cells appeared in CIN - 3 and increased in microinvasive and invasive cancer. A network between IDO and Treg cells might induce the induction of immune escape.We found immunoregulatory NK cells using leukemic mice model The surface markers of regulatory NK cells are CD94^-, acialo GMI^+, CD25^(++), CD122^(++), Thy 1, 2^(++), c - kit^+, CD3^-, DX5^+. These NK cells produced TGF - β and inhibited MEIC class II antigens on DC, and inhibited the induction of cytotoxic T cell. Interestingly, these NK cells were increased in the pregnancy uterus in mice. These NK cells were also detected in pregnancy NOD / SCID mice. We discovered these regulatory NK cells from the tumor bearing mice and pregnant mice. We confirm the similarity between tumor immunity and pregnant immunity.

胎儿是母体宿主的半异体移植，孕期应存在免疫耐受系统。耐受诱导不当可能导致流产或妊娠高血压综合征(PIH)。肿瘤细胞也能逃脱免疫攻击，因此妊娠免疫与肿瘤免疫有许多相似之处。从妊娠免疫的角度，我们发现C1D4~+CD25~+调节性T(Treg)细胞在母胎界面增加，而在流产和妊高征组降低。我们还阐明了表达吲哚胺2，3-双加氧酶(IDO)的树突状细胞(DC)和巨噬细胞在维持妊娠中起着非常重要的作用。在宫颈癌中，IDO在肿瘤细胞中表达，在宫颈上皮内瘤变(CIN)-3中有表达，在微小侵袭性癌细胞中有明显表达。有趣的是，IDO的表达仅限于侵袭前沿的癌细胞。此外，原发灶和转移灶侵袭前沿的抗原提呈细胞也表达IDO。Treg细胞表达于CIN-3，在微侵袭性癌和浸润性癌中表达增强。IDO和Treg细胞之间的网络可能诱导免疫逃逸。我们发现免疫调节性NK细胞在白血病小鼠模型中的表面标志是CD94^-，accialo Gmi^+，CD25^(++)，CD122^(++)，Thy 1，2^(++)，c-kit^+，CD3^-，DX5^+。这些NK细胞产生转化生长因子β，抑制树突状细胞表面的MEICII类抗原，并抑制细胞毒T细胞的诱导。有趣的是，这些NK细胞在小鼠怀孕的子宫中增加了。这些NK细胞也在妊娠NOD/SCID小鼠中检测到。我们从荷瘤小鼠和怀孕小鼠身上发现了这些调节性NK细胞。我们确认了肿瘤免疫和妊娠免疫之间的相似性。