| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In multiple sclerosis (MS), immunological memories to cause inflammatory demyelination are renewed and retained for long periods, and they are critically important in the lesion development during relapse and chronic progression of the disease. Recent studies demonstrated that the expression of CCR7, a chemokine receptor, is crucial in memory T cell differentiation and the subset identification. Central memory T cells (cmT, CD45RO+CCR7+) have no meaningful effector function, but are resistant to apoptosis and retain immunological memories. On the other hand, effector memory T cells (emT, CD45RO+CCR7-) efficiently migrate to sites of inflammation, secrete inflammatory cytokines, and become apoptotic.
In the present study, we analyzed dynamic state of memory T cells in MS.
1.A flow cytometric analysis of memory T cell subsets in the cerebrospinal fluid (CSF) and peripheral blood was conducted in MS, viral meningitis and control. The percentages of emT were higher in CSF than in blood in all groups. The cmT subset was significantly increased in MS than in other groups, suggesting its critical role in relapse of MS.
2.We immunohistochemically analyzed the expression and distribution of CCR7 and its ligands CCL19 and CCL21 in the cerebral white matter of autopsied brains of MS and controls. CCR7 was stained positive in some dendritic cells, activated macrophages and lymphocytes localized in the periphery of demyelinated lesions and surrounding regions, which suggests on-going antigen presentation. CCL19 was expressed on the venules around the plaques, and that might contribute to the migration of CCR7+ cells to the MS lesions. Messenges of CCR7 and CCL19 were also increased in the regions, supporting the immunohistochemical findings.
3.Memory T cell subsets were flow-cytometrically analyzed in the peripheral blood lymphocytes of MS patients stimulated with myelin basic protein twice. As time went by, the emT subset decreased, while the cmT subset increased.
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