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

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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.