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Analysis of roles of GM-CSF for proliferation and differentiation of NKT cells

GM-CSF对NKT细胞增殖分化的作用分析

基本信息

批准号：
13680773
负责人：
WATANABE Sumiko
金额：
$ 2.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680773/
关键词：
NKT Cells GM-CSF Cell differentiation Cytokine receptor T Cell receptor ES Cells Transgenic mouse 組み換えトランスジェニックマウスシグナル伝達

项目摘要

This work aimed to analyze effects of GM-CSF for proliferation and differentiation of NKT cells using transgenic mice expressing human GM-CSF receptor. GM-CSF was reported to be a maturation factor for NKT cell i. e. TCR a chain recombination inducing factor, by Dr. Taniguchi' group. We administrated GM-CSF into transgenic mice expressing human GM-CSF receptor, and found that the population of NKT cells has not been changed but the total number of spleen cells was dramatically increased. This observation suggested that GM-CSF acts as a proliferation promoting factor for NKT cells. Since we previously reported that GM-CSF induced proliferation of myeloid cells but not lymphoid cells, it is notable that NKT cells respond to GM-CSF as myeloid cells but not like lymphoid cells. The effects of GM-CSF for NKT cells was reported not only for spleen but also thymus, bone marow. We also observed that in vivo administration of GM-CSF increased NKT cells in these organs, suggesting effects of GM-CSF for NKT cells is not spleen specific. To analyze the mechanism of GM-CSF effects on NKT cells, we made double transgenic mice expressing both human GM-CSF receptor and TCRb8.2. We isolated precursor cell of NKT cells and succeeded to culture these cells in vitro. This system makes it possible to analyze molecular mechanism of NKT cell differentiation and proliferation. Furthermore, we established ES cells expressing GM-CSF receptor or its mutant stably. Using these ES cells, we are planning to make transgenic mice, and also to try in vitro differentiation of NKT cells from ES cells by using GM-CSF signals.

本工作旨在分析GM-CSF对表达人GM-CSF受体的转基因小鼠NKT细胞增殖和分化的影响。GM-CSF是NKT细胞的成熟因子。e. TCR是一种链重组诱导因子，由谷口博士的研究小组开发。我们将GM-CSF注射到转基因小鼠体内，发现NKT细胞的数量没有改变，但脾细胞的总数显著增加。这一观察结果表明，GM-CSF作为NKT细胞的增殖促进因子。由于我们先前报道GM-CSF诱导髓样细胞而不是淋巴样细胞的增殖，值得注意的是NKT细胞作为髓样细胞而不是像淋巴样细胞那样对GM-CSF应答。GM-CSF对NKT细胞的作用不仅限于脾脏，还包括胸腺、骨髓。我们还观察到，在体内施用GM-CSF增加了这些器官中的NKT细胞，这表明GM-CSF对NKT细胞的作用不是脾特异性的。为了分析GM-CSF对NKT细胞的作用机制，我们制备了同时表达人GM-CSF受体和TCR b8.2的双转基因小鼠。我们分离了NKT细胞的前体细胞，并成功地在体外培养了这些细胞。该系统的建立为深入研究NKT细胞分化和增殖的分子机制提供了可能。此外，我们建立了稳定表达GM-CSF受体或其突变体的ES细胞。利用这些ES细胞，我们正计划制造转基因小鼠，并尝试通过GM-CSF信号在体外从ES细胞分化NKT细胞。