title: Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection.
abstract: CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. Although the evolving immune environment during persistent infection reshapes established CD4 T-cell responses, the fate of naïve CD4 T cells primed in the midst of persistent infection is unclear. We demonstrate that, in marked contrast to the onset of infection, virus-specific CD4 T cells primed during an established persistent infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, virus-specific CD4 T cells primed during the established persistent infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established persistent virus infection.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Osokine
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Snell
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Cunningham
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Yamada
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Wilson
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Elsaesser
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and dbrooks@microbio.ucla.edu.
authors.forename: David
authors.initials: D
authors.lastname: Brooks
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000821:virology*; D014018:Tissue Distribution
chemical_list: D007370:Interferon Type I; D017471:Receptors, Interferon
keywords: LCMV; immunosuppression