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A Role of CC Chemokines on the Pathogenesis of Herpes Simplex Encephalomyelitis

CC趋化因子在单纯疱疹性脑脊髓炎发病机制中的作用

基本信息

批准号：
13670675
负责人：
NAKAJIMA Hideto
金额：
$ 1.6万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670675/
关键词：
herpes simplex virus encephalomyelitis chemokine Th1 Th2 cytokines Th2サイトカン

项目摘要

Th1/Th2 responses play an important role on the host defense against herpes simplex encephalomyelitis. Recently, some specific chemokines have been described as an initiator of Th1/Th2 responses. We investigated a role of monocyte chemoattractant protein (MCP)-1 in the pathogenesis of herpesvirus-induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased HSM severity in mice infected with herpes simplex virus type 2 (HSM mice). HSM severity was markedly enhanced in mice previously treated with a mixture of interleukin (IL) 4 and -10. In response to stimulation with antigen, HSM mouse cells isolated from cerebrospinal fluids (CSF cells) produced IL-4 in culture fluids, however, IL-4 production decreased in CSF cells derived from HSM mice previously treated with anti-MCP-1 antibody. A macrophage population isolated in CSF cells from HSM mice (CSF-Mphi) produced MCP-1 in culture fluids. In response to stimulation with herpesvirus antigen, T cells isolated from CSF cells from HSM mice (CSF-T cells) produced IL-4 into their culture fluids, although MCP-1 was not produced by CSF-T cells. IL-4 production by CSF-T cells was markedly enhanced when they were stimulated with viral antigen in the presence of murine recombinant MCP-1 (rMCP-1). Furthermore, IL-4 was produced in naive splenic T cells cocultured with CSF-Mphi. These results indicate that the severity of HSM is influenced by MCP-1, which stimulates Th2 responses.

Th 1/Th 2应答在宿主防御单纯疱疹病毒性脑脊髓炎中起重要作用。近年来，一些特异性趋化因子被认为是Th 1/Th 2应答的启动因子。我们研究了单核细胞趋化蛋白（MCP）-1在疱疹病毒诱导的脑脊髓炎（HSM）发病机制中的作用。抗MCP-1抗体大大降低了单纯疱疹病毒2型感染小鼠（HSM小鼠）的HSM严重程度。在先前用白细胞介素（IL）4和-10的混合物处理的小鼠中，HSM严重程度显著增强。在对抗原刺激的反应中，从脑脊液中分离的HSM小鼠细胞（CSF细胞）在培养液中产生IL-4，然而，来自先前用抗MCP-1抗体处理的HSM小鼠的CSF细胞中IL-4的产生减少。在来自HSM小鼠的CSF细胞中分离的巨噬细胞群体（CSF-Mphi）在培养液中产生MCP-1。响应于疱疹病毒抗原的刺激，从来自HSM小鼠的CSF细胞分离的T细胞（CSF-T细胞）在其培养液中产生IL-4，尽管CSF-T细胞不产生MCP-1。在鼠重组MCP-1（rMCP-1）存在下，当用病毒抗原刺激CSF-T细胞时，CSF-T细胞的IL-4产生显著增强。此外，在与CSF-Mphi共培养的幼稚脾T细胞中产生IL-4。这些结果表明，HSM的严重程度受到刺激Th 2应答的MCP-1的影响。