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

我们已经发现了一种具有DDD背景的突变小鼠品系，plt（淋巴结T细胞缺乏）小鼠，其中T细胞不能迁移到淋巴结、派伊尔集合淋巴结或脾白色髓中的T细胞区域。抗原刺激的树突状细胞也不进入T细胞区。这些小鼠缺乏次级淋巴组织趋化因子（SLC）的表达，这是SLC基因缺失的结果，我们研究了这些突变小鼠发生实验性变态反应性脑脊髓炎（EAE）的情况。当这些小鼠用髓鞘碱性蛋白（MBP）免疫时，EAE的发生频率低于对照小鼠。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远低于对照小鼠。为了进一步分析，我们建立了SLC基因缺失的C57 BL/6小鼠，并用MOG 35 -55肽免疫。C57 BL/6-plt小鼠对EAE的发展也有抵抗力。MBP或MOG特异性T细胞在EAE的发展中起着关键作用。MBP或MOG免疫的plt小鼠可能未诱导出这些T细胞。然而，这种可能性似乎不太可能，因为在这些小鼠中，用蛋白抗原引发的体内T细胞不受影响。这些发现表明趋化因子能够控制EAE的发展。我们的发现也提出了一种可能性，即趋化因子可能能够控制多发性硬化症。

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.