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 - / - 小鼠和抹布 - / - 小鼠中鉴定出NK-T细胞的直接前体。这些是NK1.1^+，TCR^ - 和与NK细胞相似的独特表型。在用PMA +离子霉素刺激后，这些前体在新生儿胸腺器官培养中分化为NK-T细胞。2。在2C转基因小鼠中发现了NK-T细胞的正常群体，其具有MHC类的TCRI。在负MHC类中。在负MHC背景（H-2^d）中，NK-T细胞的主要群体是Cd4，d doubled Backdack（H-2）的主要背景（H-2）。积极的。这些NK-T细胞用体内抗CD3 mAb刺激后产生大量的IFN-γ，但没有产生IL-4。在中性背景（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。这些发现表明，在MHC的影响下开发了一定的NK-T细胞。3。在合成性混合淋巴细胞反应（SMLR）中检测到NK-T细胞的增殖，其中纯化的树突状细胞是刺激剂。 NK-T细胞在SMLR中重新调节的抗原系统现在正在研究中。4。在新西兰小鼠菌株中发现了与年龄相关的NK-T细胞比例的降低，自身免疫性易于菌株，但在另一种自身免疫性菌株中却没有。这些下降似乎与NK-T细胞的高完成敏感性有关。5.使用Aly/Aly小鼠，表明胸腺髓质上皮细胞对于NK-T细胞的产生是必不可少的。