title: Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4⁺ T cells.
abstract: Type I interferons (IFNs) have the dual ability to promote the development of the immune response and exert an anti-inflammatory activity. We analyzed the integrated effect of IFN-α, TCR signal strength, and CD28 costimulation on human CD4⁺ T-cell differentiation into cell subsets producing the anti- and proinflammatory cytokines IL-10 and IFN-γ. We show that IFN-α boosted TCR-induced IL-10 expression in activated peripheral CD45RA⁺CD4⁺ T cells and in whole blood cultures. The functional cooperation between TCR and IFN-α efficiently occurred at low engagement of receptors. Moreover, IFN-α rapidly cooperated with anti-CD3 stimulation alone. IFN-α, but not IL-10, drove the early development of type I regulatory T cells that were mostly IL-10⁺ Foxp3⁻ IFN-γ⁻ and favored IL-10 expression in a fraction of Foxp3⁺ T cells. Our data support a model in which IFN-α costimulates TCR toward the production of IL-10 whose level can be amplified via an autocrine feedback loop.
authors.affiliation: Department of Immunology, Unit of Cytokine Signaling, Institut Pasteur, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Corre
authors.forename: Julie
authors.initials: J
authors.lastname: Perrier
authors.forename: Margueritte
authors.initials: M
authors.lastname: El Khouri
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerboni
authors.forename: Sandra
authors.initials: S
authors.lastname: Pellegrini
authors.forename: Frédérique
authors.initials: F
authors.lastname: Michel
mesh_terms: D018106:CD28 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D011485:Protein Binding; D020239:Receptor Cross-Talk / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018836:Inflammation Mediators; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens
keywords: CD4+ T cells; IFN-α/β; IL-10; T helper cells; Tr1 cells