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Abnormalities of T lymphocyte subsets in systemic sclerosis and analyses of the inducing cytokines

系统性硬化症T淋巴细胞亚群异常及诱导细胞因子分析

基本信息

批准号：
09670891
负责人：
SASAKI Tetsuo
金额：
$ 0.77万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670891/
关键词：
systemic sclerosis T lymphocyte subsets cytokine tight-skin mouse flow cytometry interleukin 12 interleukin 4 antinuclear antibody T リンパ球 tight skin マウス皮膚線維化インターフェロンγ 遺伝子治療 Tリンパ球 IL-12 IL-4 線維化抑制発現プラスミド

项目摘要

We examined the frequencies of interleukin (IL)-4 or IL-2 producing CD4^+ or CD8^+T cells in peripheral blood mononuclear cells (PBMC_5) from patients with systemic sclerosis (SSc). The frequency of CD4^+T cells was negatively correlated with duration of SSc, whereas the frequency of CD8^+T cells was not correlated with duration. The frequencies of IL-4 producing (IL-4^+) cells in CD4^+T cells and in CD8^+T cells from the patients with SSc were both significantly higher than those from the healthy controls. In contrast, the frequencies of IL-2 producing (IL-2^+) cells in CD4^+T cells and in CD8^+T cells from patients with SSc were both significantly lower than that from the healthy controls. Further, the ratios of IL-4^+/IL-4^+ + IL-2^+ in CD4^+T cells and in CD8^+T cells were both negatively correlated with the disease duration of SSc. These results suggest that type 2 cytokine-producing T cells, not only CD4^+T cells but also CD8^+T cells, have important roles in the pathogenesis of … More SSc, especially in the early phase of SSc. We then examined the effect of IL-12 encoding plasmid (pCAGGSIL-12) on the disease progression of Tsk/+ mice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscularly 7 times with 3 weeks intervals into Tsk/+ mice. One week after the last injection, pCAGGSIL-12 administered Tsk/+ mice exhibited a marked decrease in the skin thickness compared with the mice treated with pCAGGS vector. The serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 treated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These results indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficial effects in preventing the collagen accumulation in the skin and suppressing the autoimmunity via improvement of Th1/Th2 balance. The present study suggests that the IL-12 encoding plasmid administration might have a therapeutic effect on systemic sclerosis. Less

我们检测了系统性硬化症（SSc）患者外周血单个核细胞（PBMC_5）中产生白细胞介素（IL）-4或IL-2的CD 4 ^+或CD 8 ^+T细胞的频率。CD 4 ^+T细胞的频率与SSc的持续时间呈负相关，而CD 8 ^+T细胞的频率与持续时间无关。SSc患者的CD 4 ^+T细胞和CD 8 ^+T细胞中产生IL-4（IL-4^+）细胞的频率均显著高于健康对照组。相比之下，SSc患者的CD 4 ^+T细胞和CD 8 ^+T细胞中产生IL-2（IL-2^+）细胞的频率均显著低于健康对照组。此外，CD 4 ^+T细胞和CD 8 ^+T细胞中IL-4 ^+/IL-4^+ + IL-2^+的比值均与SSc的病程呈负相关。这些结果表明，产生2型亮氨酸的T细胞，不仅是CD 4 ^+T细胞，而且是CD 8 ^+T细胞，在白血病的发病机制中具有重要作用。 ...更多信息尤其是在SSc的早期。然后，我们检查了IL-12编码质粒（pCAGGSIL-12）对Tsk/+小鼠疾病进展的影响。将pCAGGSIL-12质粒或pCAGGS亲本载体以3周间隔肌肉注射到Tsk/+小鼠中7次。最后一次注射后一周，与用pCAGGS载体处理的小鼠相比，施用pCAGGSIL-12的Tsk/+小鼠表现出皮肤厚度的显著降低。在pCAGGSIL-12处理的小鼠中，抗核抗体的血清水平降低。来自pCAGGSIL-12质粒处理的小鼠的脾细胞的IL-4产生显著低于来自载体处理的小鼠。这些结果表明，将pCAGGSIL-12给予Tsk/+小鼠，通过改善Th 1/Th 2平衡，在防止皮肤中胶原积聚和抑制自身免疫方面具有有益效果。目前的研究表明，IL-12编码质粒的管理可能有系统性硬化症的治疗效果。少