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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-/-小鼠中鉴定了NK-T细胞的直接前体。这些细胞是NK 1.1 ^+、TCR^-，表现出与NK细胞相似的独特表型。在PMA +离子霉素刺激下，这些前体细胞在新生胸腺器官培养中分化为NK-T细胞。2.在具有MHC I类特异性TCR的2C转基因小鼠中发现正常的NK-T细胞群。在阴性MHC背景（H-2 ^d）中，主要NK-T细胞群体为CD 4，8双阴性，而在阳性背景（H-2 ^b）中，主要NK-T细胞为CD 8单阳性。这些NK-T细胞在体内用抗CD 3 mAb刺激后产生大量IFN-γ，但不产生IL-4。在中性背景（H-2 ^k）中不产生NK-T细胞。CD 1分子不参与NK-T细胞的选择，说明NK-T细胞的形成受MHC分子的影响，而不受CD 1分子的影响。3.在以纯化的树突状细胞为刺激物的同系混合淋巴细胞反应（SMLR）中，可检测到NK-T细胞的增殖。4.在新西兰品系的自身免疫易感小鼠中发现了与免疫缺陷相关的NK-T细胞比例的降低，但在另一种自身免疫易感品系1 pr小鼠中没有发现。这些减少似乎与NK细胞的高补体敏感性有关。5.用aly/aly小鼠研究表明，胸腺髓质上皮细胞是NK细胞产生所必需的。