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A study on differentiation and function of NK-T cells that regulate autoimmune diseases

调节自身免疫性疾病的NK-T细胞的分化和功能研究

基本信息

批准号：
12470050
负责人：
ONOE Kazunori
金额：
$ 10.05万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470050/
关键词：
NK-T cell autoimmune cytokine Th1 and Th2 CD8 molecule syngenic MLR 前駆細胞 ZAP-70 胸腺器官培養 2Cトランスジェニックマウス

项目摘要

1.Direct precursors of NK-T cells were identified in ZAP-70-/-mice and RAG-/-mice. These were NK1.1^+,TCR^-and exhibited a unique phenotype similar to NK cells. Upon stimulation with PMA +ionomycin, these precursors differentiated into NK-T cells in a neonatal thymic organ culture.2.A normal population of NK-T cells were found in 2C transgenic mice with TCR specific for MHC class I. In the negative MHC background(H-2^d) the major population of NK-T cells were CD4,8 double negative, whereas in the positive background(H-2^b) the major NK-T cells were CD8 single positive. These NK-T cells produced a large amount of IFN-γ but not IL-4 upon stimulation with anti-CD3 mAb in vivo. No NK-T cells were generated in the neutral background(H-2^k). CD1 molecules appeared not to be involved in the selection of NK-T cells.These findings demonstrate that a certain population of NK-T cells has been developed under the influence of MHC but not CD1 molecules.3.Proliferation of NK-T cells was detected in syngeneic mixed lymphocyte response(SMLR) where purified dendritic cells were stimulators. The antigen system that NK-T cells recongnize in the SMLR is now under investigation.4.Age-related decrease in the proportion of NK-T cells was found in New Zealand strains of mice, autoimmune prone a strains, but not in another autoimmune prone strain, 1pr mice. It appeared that these decreases were associated with the high complement sensitivity of NK-T cells.5.Using aly/aly mice it shown that thymic medullary epithelial cells were indispensable to generation of NK-T cells.

1.在ZAP-70-/-小鼠和RAG-/-小鼠中发现了NK-T细胞的直接前体细胞。这些细胞是NK1.1^+，TCR^-，表现出与NK细胞相似的独特表型。在PMA+离子霉素的刺激下，这些前体细胞在新生胸腺器官培养中分化为NK-T细胞。2.在MHC I类特异性TCR转基因小鼠中，2C转基因小鼠的NK-T细胞群正常。在MHC阴性背景(H-2^d)中，NK-T细胞以CD4、8双阴性为主，而在阳性背景(H-2^b)中，主要NK-T细胞为CD8单阳性。在体内，这些NK-T细胞在抗CD3mAb刺激下产生大量的干扰素-γ，而不产生IL-4。中性背景(H-2^k)中未产生NK-T细胞。CD1分子似乎不参与NK-T细胞的选择。这些结果表明，在MHC的影响下，一定数量的NK-T细胞已经形成，但CD1分子不参与。3.在以纯化的树突状细胞为刺激因子的同基因混合淋巴细胞反应(SMLR)中，检测到NK-T细胞的增殖。NK-T细胞在SMLR中识别的抗原系统目前正在研究中。4.在新西兰品系的自体免疫倾向A品系小鼠中，发现NK-T细胞比例随年龄的增长而下降，但在另一种自体免疫倾向品系1PR小鼠中没有发现。这可能与NK-T细胞对补体的高度敏感性有关。5.通过对Aly/Aly小鼠的研究表明，胸腺髓质上皮细胞对于NK-T细胞的产生是不可或缺的。