LPS对MRL/MpJ小鼠脾T细胞表达TLR4和TNFα的影响

研究Toll样受体 4 (TLR4 )在MRL/MpJ小鼠脾细胞的表达状况和革兰阴性菌脂多糖 (LPS )刺激后TLR4的表达变化以及对TNF α产生的影响。MRL/MpJ小鼠经腹腔注射LPS后在不同时间取脾细胞 ,用三色荧光标记流式细胞仪技术检测小鼠脾T细胞TLR4的表达情况 ,并与BALB/c小鼠作对照 ;通过RT PCR观察LPS刺激前后脾T细胞TNF αmRNA的表达变化。结果表明TLR4在MRL/MpJ小鼠CD3+ CD4 + T细胞和CD3+ CD8+ T细胞中均有表达 ;但TLR4 + /CD4 + 细胞表达仅BALB/c小鼠的 33% ,在受LPS刺激后 ,MRL/MpJ鼠CD4 + T细胞TLR4升高时间较BALB/c小鼠延迟 ;CD8+ T细胞TLR4在LPS刺激前后无明显变化 ;脾细胞TNF αmRNA水平升高亦延迟。通过对干燥综合征样自身免疫病鼠模型MRL/MpJ小鼠脾T细胞TLR4的表达及功能研究 ,将有助于认识天然免疫和获得性免疫间的联系和感染在自身免疫病发病中的作用。

Changes of Expression of TLR4 and TNF-α Induced by LPS in the Splenic T Cells of MRL/MpJ Mice

To observe the expression of TLR4 in the splenic lymphocytes of MRL/MpJ mice and changes of TLR4 expression and TNF-α mRNA production induced by LPS. MRL/MpJ mices responded to the intraperitoneal injection of LPS were sacrificed in 6, 12, 18, 36, 48 hours respectively. TLR4 was analyzed in the splenic lymphocytes of mice by flow cytometry analysis and changes of TNF-α mRNA were detected by RT-PCR. BALB/c mouse were used as controls. It was found that TLR4 were detected in CD3+、CD4+、CD8+T lymphocytes of MRL/MpJ splenic cells and the TLR4/CD4 double positive cells were significantly lower in MRL/MpJ mice than BALB/c mice, only accounting for 33% of the BALB/c mice. The TLR4/CD8 double positive cells were similar in these two kinds of mouse. After treatment with LPS, the delayed up-regulation of TLR4 was detected in CD4+ T cells of MRL/MpJ mice, whereas no significant differences were detected in CD8+ T cells. The up-regulations of TNF-α mRNA were also delayed in splenic cells of MRL/MpJ mice. The expression of TLR4 and the responsibility to LPS were lower in CD4+ splenic T cells of MRL/MpJ mice and up-regulation of TNF-α mRNA were also delayed in the splenic cells. It suggests that this Sjogren syndrome like autoimmune disease mice model will have a potential value in understanding the relationship between the innate immunity and acquired immunity as well as the role of infection to the autoimmune disease.