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)患者外周血单个核细胞(PBMC_5)中产生IL-4或IL-2的CD4~+或CD8~+T细胞的频率。CD8+T细胞频率与病程无关，而与病程呈负相关。SSC患者外周血中CD_4~+T细胞和CD_8~+T细胞产生IL-4细胞的频率均显著高于健康对照组。而SSC患者外周血中CD8+T细胞和CD8+T细胞中产生IL-2细胞的频率均显著低于正常对照组。此外，CD8+T细胞和CD8+T细胞中IL-4/IL-4、IL-2的比值与SSC的病程呈负相关。这些结果表明，产生2型细胞因子的T细胞，不仅是CD4T细胞，也是CD8T细胞，在…的发病机制中起着重要的作用更多的SSC，特别是在SSC的早期阶段。然后，我们检测了IL-12编码基因(pCAGGsIL-12)对TSK/小鼠疾病进展的影响。将pCAGGSIL12或pCAGGS亲本载体肌肉注射TSK小鼠，间隔3周，共7次。最后一次注射后一周，与pCAGGGS载体组相比，pCAGGSIL-12组TSK/小鼠的皮肤厚度明显减少。经pCAGGSIL12处理的小鼠血清抗核抗体水平降低。PCAGGSIL12基因治疗的小鼠脾细胞产生IL-4的能力明显低于载体治疗的小鼠。这些结果表明，pCAGGsIL-12通过改善Th1/Th2平衡，预防皮肤胶原堆积，抑制自身免疫功能。本研究提示IL-12编码基因可能对系统性硬化症有治疗作用。较少

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