Differential regulation of Th1 responses and CD154 expression in human CD4+ T cells by IFN-α

Abstract

SUMMARY Like interleukin (IL)-12, interferon (IFN)-α has been shown to play an important role in inducing human Th1 responses. Recent studies have shown that human Th1 responses driven by IL-12 are associated with enhanced expression of CD154. 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. Highly purified CD4+ T cells from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-α and IL-12 in the complete absence of accessory cells. IFN-α suppressed CD154 protein and mRNA expression in CD4+ T cells at the initial phase of activation with immobilized anti-CD3, but enhanced it in the subsequent maturation phase 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 even in the presence of stimulation with anti-CD28, but enhanced it in the presence of IL-12. Accordingly, IFN-α enhanced IL-12Rβ2 mRNA expression in anti-CD3-stimulated CD4+ T cells. Neither IFN-α nor IL-12 influenced the stability of CD154 mRNA in anti-CD3-activated CD4+ T cells. These results indicate that IFN-α by itself enhances CD154 expression in CD4+ T cells 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 and that the induction of Th1 responses and CD154 expression in human CD4+ T cells might be regulated through different mechanisms.