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

我们检测了系统性硬化症（SSc）患者外周血单核细胞（PBMC_5）中产生CD4^+或CD8^+T细胞的白细胞介素(IL)-4或IL-2的频率。CD4^+T细胞频率与SSc持续时间呈负相关，而CD8^+T细胞频率与SSc持续时间无相关。SSc患者CD4^+T细胞和CD8^+T细胞中IL-4生成（IL-4^+）细胞的频率均显著高于健康对照组。相比之下，SSc患者CD4^+T细胞和CD8^+T细胞中IL-2生成（IL-2^+）细胞的频率均显著低于健康对照组。CD4^+T细胞和CD8^+T细胞中IL-4^+/IL-4^+ + IL-2^+比值与SSc病程均呈负相关。这些结果表明，产生2型细胞因子的T细胞，不仅是CD4^+T细胞，还有CD8^+T细胞，在SSc的发病机制中起重要作用，特别是在SSc的早期阶段。然后，我们检测了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亲代载体肌内注射7次，间隔3周。在最后一次注射pCAGGSIL-12一周后，与pCAGGS载体处理的小鼠相比，给予pCAGGSIL-12的Tsk/+小鼠的皮肤厚度明显减少。pCAGGSIL-12处理小鼠血清抗核抗体水平降低。pCAGGSIL-12质粒处理的小鼠脾细胞IL-4产量明显低于载体处理的小鼠。这些结果表明，pCAGGSIL-12通过改善Th1/Th2平衡，对Tsk/+小鼠具有抑制皮肤胶原积累和抑制自身免疫的有益作用。本研究提示IL-12编码质粒给药可能对系统性硬化症有治疗作用。少

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