title: IRF3 deficiency impacts granzyme B expression and maintenance of memory T cell function in response to viral infection.
abstract: The role of interferon regulatory factor 3 (IRF3) in the innate immune response to infection has been well studied. However, less is known about IRF3 signaling in shaping the adaptive T cell response. To determine the role of IRF3 in the generation and maintenance of effective anti-viral T cell responses, mice deficient in IRF3 were infected with a potentially persistent virus, Theiler's murine encephalomyelitis virus (TMEV) or with a model acute infection, influenza A virus (IAV). IRF3 was required to prevent TMEV persistence and induce robust TMEV specific effector T cell responses at the site of infection. This defect was more pronounced in the memory phase with an apparent lack of TMEV-specific memory T cells expressing granzyme B (GrB) in IRF3 deficient mice. In contrast, IRF3 had no effect on antigen specific T cell responses at the effector stage during IAV infection. However, memory T cell responses to IAV were also impaired in IRF3 deficient mice. Furthermore, addition of cytokines during peptide restimulation could not restore GrB expression in IRF3 deficient memory T cells. Taken together, IRF3 plays an important role in the maintenance of effective anti-viral T cell memory responses.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, USA.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Moore
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Vogel
authors.affiliation: Nebraska Center for Virology, University of Nebraska-Lincoln, USA; Department of Oral Biology, University of Nebraska Medical Center, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, USA. Electronic address: dbrown7@unl.edu.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Brown
mesh_terms: D000818:Animals; D053804:Granzymes / Q000276:immunology / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency*; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017945:Theilovirus / Q000276:immunology* / Q000378:metabolism
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D053804:Granzymes
keywords: Cytokines; Influenza A virus; Interferon regulatory factor-3; T cell memory; T cells; Theiler's murine encephalomyelitis virus