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MECHANISMS FOR THE INHIBITION OF DEVELOPMENT IN ENCEPHALOMYELITIS IN MICE LACKING THE EXPRESSION OF A CHEMOKINE REQUIRED FOR T CELL MIGRATION.

抑制缺乏 T 细胞迁移所需趋化因子表达的小鼠脑脊髓炎发展的机制。

基本信息

批准号：
10670606
负责人：
KAKIUCHI Terutaka
金额：
$ 1.73万
依托单位：
TOHO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670606/
关键词：
Multiple Sclerosis Encephalomyelitis EAE T cell Homing plt Chemokine SLC 脳脊髄膜炎

项目摘要

We have found a mutant mouse strain with DDD background, plt (paucity of lymph node T cells) mouse, in which T cells are unable to migrate into the T cell areas in lymph nodes, Peyer's patches, or spleen white pulp. Antigen-stimulated dendritic cells do not entry into the T cell zones either. These mice lack the expression of secondary lymphoid tissue chemokine (SLC)s, which results from the deletion of SLC gene.We examined the development of experimental allergic encephalomyelitis (EAE) in these mutant mice. When these mice were immunized with myelin basic protein (MBP), EAE developed with a fewer frequency than in the control mice. Even when the MBP-immunized mutant mice developed EAE, the clinical score in these mice was much lower than in the control mice. For further analysis, we established C57BL/6 mice with the deletion of SLC gene, and immunized with MOG35-55 peptide. C57BL/6-plt mice were also resistant to the development of EAE. MBP- or MOG-specific T cells play a critical role to develop EAE. It might be possible that these T cells were not induced in plt mice immunized with MBP or MOG. However, this possibility seems unlikely, since in vivo T cell-priming with a protein antigen was not affected in these mice. These findings suggest that a chemokine is able to control the EAE development. Our findings also raised a possibility that a chemokine might be able to control multiple sclerosis.

我们发现了一种具有DDD背景的突变小鼠品系PLT(Lapucity Of Lapnode T Cells)，在该品系中，T细胞不能迁移到淋巴结、Peyer氏斑或脾白髓中的T细胞区。抗原刺激的树突状细胞也不会进入T细胞区。这些突变小鼠缺乏次级淋巴组织趋化因子S的表达，次级淋巴组织趋化因子基因缺失是次级淋巴组织趋化因子基因缺失的结果。当这些小鼠被髓鞘碱性蛋白(MBP)免疫时，发生EAE的频率比对照组小鼠少。即使当MBP免疫的突变小鼠发生EAE时，这些小鼠的临床评分也比对照小鼠低得多。为了进一步分析，我们建立了SLC基因缺失的C57BL/6小鼠，并用MOG35-55肽免疫。C57BL/6-PLT小鼠对EAE的发生也具有抵抗力。MBP或MOG特异性T细胞在EAE的发生中起着关键作用。在MBP或MOG免疫的PLT小鼠中，这些T细胞可能没有被诱导。然而，这种可能性似乎不太可能，因为在体内，用蛋白质抗原启动T细胞在这些小鼠中没有受到影响。这些发现表明趋化因子能够控制EAE的发展。我们的发现还提出了一种可能性，即趋化因子可能能够控制多发性硬化症。