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

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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.