| Project/Area Number |
17390447
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | University of Toyama |
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Principal Investigator |
SAITO Shigeru University of Toyama, Obstetrics and Gynecology, Professor (30175351)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Takafumi University of Toyama, Obstetrics and Gynecology, Associate Professor (20303969)
WAKASUGI Satomi University of Toyama, Obstetrics and Gynecology, Assistant Professor (90361956)
酒井 正利 富山大学, 附属病院, 助教授 (90242502)
日高 隆雄 富山大学, 附属病院, 講師 (70283083)
佐々木 泰 富山大学, 附属病院, 助手 (60324050)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,270,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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