Differential effects of IFN-α on the expression of various TH2 cytokines in human CD4+ T cells

Background: In both human subjects and mice, T helper cells are classified into 2 subsets, T(H)1 and T(H)2 cells, on the basis of the cytokines they produce. Although IFN-alpha has been shown to enhance human T(H)1 responses, its influences on human T(H)2 responses have not yet been fully characterized. In addition, the mechanism for induction of T(H)1 responses by IFN-alpha has not been fully delineated. Objective: The present study was undertaken to explore the direct effects of IFN-alpha on the expression of various cytokines in human CD4(+) T cells with a system using immobilized anti-CD3, which permits activation of CD4(+) T cells in the complete absence of accessory cells. Methods: Highly purified CD4(+) T cells obtained from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-alpha and IL-12 in the complete absence of accessory cells. The production of cytokines was estimated by means of ELISA. The expression of mRNA for various cytokines, as well as transcription factors, was evaluated by using quantitative PCR. Results: IFN-alpha enhanced IL-4 protein and mRNA expression in immobilized anti-CD3-stimulated CD4(+) T cells, irrespective of the presence of IL-12, whereas IFN-alpha suppressed the expression of IL-5 and IL-13. Of note, IFN-alpha enhanced the expression of mRNA for c-Maf, T-bet, and Fox-P3, irrespective of the presence of IL-12, but not that for GATA-3, in anti-CD3-stimulated CD4(+) T cells. Conclusion: These results indicate that IFN-alpha enhances the induction of T(H)1 responses through upregulation of T-bet mRNA expression, as well as the induction of T(H)2 responses through upregulation of c-Maf mRNA expression, followed by IL-4 expression. Moreover, the data also suggest that IFN-alpha might suppress the expression of IL-5 and IL-13 in differentiated T(H)2 cells.