title: The role of Stat4 in species-specific regulation of Th cell development by type I IFNs.
abstract: Type I IFNs (IFN-alpha/beta), in addition to IL-12, have been shown to play an important role in the differentiation of human, but not mouse, Th cells. We show here that IFN-alpha/beta act directly on human T cells to drive Th1 development, bypassing the need for IL-12-induced signaling, whereas IFN-alpha cannot substitute IL-12 for mouse Th1 development. The molecular basis for this species specificity is that IFN-alpha/beta activate Stat4 in differentiating human, but not mouse, Th cells. Unlike IL-12, which acts only on Th1 cells, IFN-alpha/beta can activate Stat4 not only in human Th1, but also in Th2 cells. However, restimulation of human Th2 lines and clones in the presence of IFN-alpha does not induce the production of IFN-gamma. These results suggest that activation of Stat4, which is necessary for the differentiation of naive T cells into polarized Th1 cells, is not sufficient to induce phenotype reversal of human Th2 cells.
authors.affiliation: Roche Milano Ricerche, Milan, Italy. lars.rogge@roche.com
authors.forename: L
authors.initials: L
authors.lastname: Rogge
authors.forename: D
authors.initials: D
authors.lastname: D'Ambrosio
authors.forename: M
authors.initials: M
authors.lastname: Biffi
authors.forename: G
authors.initials: G
authors.lastname: Penna
authors.forename: L J
authors.initials: LJ
authors.lastname: Minetti
authors.forename: D H
authors.initials: DH
authors.lastname: Presky
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: F
authors.initials: F
authors.lastname: Sinigaglia
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D013045:Species Specificity; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology*; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12