title: Differential regulation of Th1 responses and CD154 expression in human CD4+ T cells by IFN-alpha.
abstract: Like interleukin (IL)-12, interferon (IFN)-alpha 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-alpha 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-alpha and IL-12 in the complete absence of accessory cells. IFN-alpha 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-alpha by itself did not enhance IFN-gamma 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-alpha enhanced IL-12Rbeta2 mRNA expression in anti-CD3-stimulated CD4+ T cells. Neither IFN-alpha nor IL-12 influenced the stability of CD154 mRNA in anti-CD3-activated CD4+ T cells. These results indicate that IFN-alpha by itself enhances CD154 expression in CD4+ T cells independently of the induction of IFN-gamma mRNA expression. The data also suggest that the optimal induction of human Th1 responses by IFN-alpha 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.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shibuya
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: A
authors.initials: A
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Hirohata
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000494:pharmacology*; D018664:Interleukin-12 / Q000032:analysis; D008213:Lymphocyte Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D023201:CD40 Ligand; D018664:Interleukin-12