Molecular analysis of the abnormal expression of CD 154 in T cells as a mechanism of induction of autoinimune disease.

与IL-12一样，IFN-α也在人类Th1反应中发挥重要作用。虽然IL-12增强CD154在人T细胞上的表达，但IFN-α的作用尚未被阐明。本研究检测了IFN-α对人CD4+ T细胞中CD154表达的影响，特别关注了与Th1反应的关系。IFN-α在固定抗cd3激活CD4+ T细胞的初始阶段抑制CD154蛋白和mRNA的表达，但此后无论IL-12是否存在，IFN-α都能增强CD154蛋白和mRNA的表达。相比之下，在没有IL-12的情况下，IFN-α本身并没有增强CD4+ T细胞中IFN-γ的产生或mRNA的表达，而在IL-12存在的情况下，IFN-α却增强了IFN-γ的产生或mRNA的表达。在抗cd3激活的CD4+ T细胞中，IFN-α或IL-12均不影响CD154 mRNA的稳定性。使用含有CD154启动子区域的报告载体进行的荧光素酶分析表明，IFN-α和IL-12都上调了CD154 mRNA的转录。这些结果表明，IFN-α通过上调CD154 mRNA的转录而不依赖于诱导IFN-γ mRNA的表达，直接增强CD154在CD4+ T细胞中的表达。这些数据还表明，IFN-α诱导人类Th1反应的最佳方式可能需要IL-12的存在。

Like IL-12, IFN-α has been found to play an important role in human Th1 responses. Whereas IL-12 enhances CD154 expression on human T cells, the effect of IFN-α has not been elucidated. The present study examined the effects of IFN-α on CD154 expression in human CD4+ T cells, with special attention to the relationship with Th1 responses. IFN-α suppressed CD154 protein and mRNA expression in CD4+ T cells at the initial phase of activation with immobilized anti-CD3, but thereafter enhanced it irrespective of the presence of IL-12. By contrast, IFN-α by itself did not enhance IFN-γ production or mRNA expression in CD4+ T cells in the absence of IL-12, whereas it enhanced it in the presence of IL-12. Either IFN-α or IL-12 did not influence the stability of CD154 mRNA in anti-CD3 activated CD4+ T cells. Rather luciferase assays using a reporter vector containing the CD154 promoter region demonstrate that both IFN-α and IL-12 upregulate the transcription of CD154 mRNA. These results indicate that IFN-α directly enhances CD154 expression in CD4+ T cells by up-regulating the transcription of CD154 mRNA independently of the induction of IFN-γ mRNA expression. The data also suggest that the optimal induction of human Th1 responses by IFN-α might require the presence of IL-12.