title: Type I IFNs inhibit human dendritic cell IL-12 production and Th1 cell development.
abstract: We have investigated the role of type I IFNs (IFN-alpha and -beta) in human T cell differentiation using anti-CD3 mAb and allogeneic, in vitro-derived dendritic cells (DC) as APCs. DC were very efficient activators of naive CD4+ T cells, providing necessary costimulation and soluble factors to support Th1 differentiation and expansion. Addition of IFN-alphabeta to DC/T cell cultures resulted in induction of T cell IL-10 production and inhibition of IFN-gamma, TNF-alpha, and LT secretion. Diminished T cell IFN-gamma production correlated with IFN-alphabeta-mediated inhibition of the p40 chain of the IL-12 heterodimer secreted by DC. Suppression of p40 IL-12 and IFN-gamma was not due to increased levels of IL-10 in these cultures, and production of IFN-gamma could be restored by exogenous IL-12. These data indicate that type I IFNs inhibit DC p40 IL-12 expression, which is required for development of IFN-gamma-producing CD4+ T cells. Furthermore, when T cells were restimulated without IFN-beta, these cells induced less p40 IL-12 from DC, suggesting that the functional properties of T cells may regulate DC function. Thus, IFN-alphabeta inhibits both IL-12-dependent and independent Th1 cytokine production and provides a mechanism for inhibition of IL-12-mediated immunity in viral infections.
authors.affiliation: Department of Pathology, University of Chicago, IL 60637, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: McRae
authors.forename: R T
authors.initials: RT
authors.lastname: Semnani
authors.forename: M P
authors.initials: MP
authors.lastname: Hayes
authors.forename: G A
authors.initials: GA
authors.lastname: van Seventer
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta