Analysis of interaction of CD40 and CD40-ligand in autoimmune diseases and research for regulation drugs.

在系统性红斑狼疮(SLE)患者中，CD154(CD40配体)在活化的CD4阳性T细胞上的表达是短暂的，并且受到抗原特异性免疫反应的严格调控，并且在SLE患者中增加并延长。我们通过检测PMA和离子霉素刺激的CD154阳性T细胞中CD154蛋白和mRNA的表达来研究CD154表达的调节，并证实了CD154在SLE T细胞中的表达增加和延长。在PMA和离子霉素刺激后，用转录抑制剂放线菌素D处理SLE T细胞，发现活化的SLE T细胞CD154mRNA的稳定性比对照组显著增加。然而，在3‘非翻译区(3’UTR)没有发现突变或异常序列，包括富含AU的元件和富含Cu的序列，但它们部分参与了CD154 mRNA转录后稳定性的调节。体外培养96h后，CD154mRNA的表达失稳，导致活化的SLE T细胞表面表达相应降低和正常化。我们认为SLE患者T细胞表面CD154的表达可能增加并延长，其表达的稳定与体内持续刺激有关。

The expression of CD154(CD40-ligand) on activated CD4-positive T cells is known to be transient and tightly regulated for antigen-specific immune responses, and is increase, and prolonged among patients with systemic lupus erythematosus(SLE). We investigated the regulation of CD154 expression by determining the protein and mRNA expression with PMA and ionomycin stimulation in CD4-positive T cells, and confirmed their increase and prolongation in SLE T cells. Treatment with actinomycin D, a transcription inhibitor, after PMA and ionomycin stimulation was performed, and the findings revealed that the stability of CD154 mRNA increased significantly in activated SLE T cells compared with that of controls. However, alternations or abnormal sequences were not identified in the 3' untranslated region(3'UTR), including AU-rich elements and CU-rich sequences, while their partial involvement in the post-transcriptional regulation of CD154 mRNA stability has been reported. With 96h culture in vitro, the destabilization of CD154 mRNA was demonstrated, resulting in a corresponding decrease and normalization of surface expression on activated SLE T cells. We suggest that the CD154 expression on T cells from SLE patients may be increased and prolonged, with mRNA stabilization being related to a continuous stimulation in vivo.