title: The Th1 life cycle: molecular control of IFN-γ to IL-10 switching.
abstract: Control of IFN-γ-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-γ, during Th1 lineage differentiation. Targeting this Th1 cell IFN-γ to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases. In this review, the molecular pathways that regulate IFN-γ versus IL-10 expression in Th1 cells are examined, with focus on the role of complement regulator and T cell co-stimulatory molecule CD46, and also discussed are challenges and controversies in the field.
authors.affiliation: Academic Department of Rheumatology, Division of Immunology, Infection and Inflammatory Diseases, King's College School of Medicine, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cope
authors.forename: Gaelle
authors.initials: G
authors.lastname: Le Friec
authors.forename: John
authors.initials: J
authors.lastname: Cardone
authors.forename: Claudia
authors.initials: C
authors.lastname: Kemper
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma