Interferon-β suppresses murine Th1 cell function in the absence of antigen-presenting cells

PLoS One. 2015 Apr 17;10(4):e0124802. doi: 10.1371/journal.pone.0124802. eCollection 2015.


Interferon (IFN)-β is a front-line therapy for the treatment of the relapsing-remitting form of multiple sclerosis. However, its immunosuppressive mechanism of function remains incompletely understood. While it has been proposed that IFN-β suppresses the function of inflammatory myelin antigen-reactive T cells by promoting the release of immunomodulatory cytokines such as IL-27 from antigen-presenting cells (APCs), its direct effects on inflammatory CD4+ Th1 cells are less clear. Here, we establish that IFN-β inhibits mouse IFN-γ+ Th1 cell function in the absence of APCs. CD4+ T cells express the type I interferon receptor, and IFN-β can suppress Th1 cell proliferation under APC-free stimulation conditions. IFN-β-treated myelin antigen-specific Th1 cells are impaired in their ability to induce severe experimental autoimmune encephalomyelitis (EAE) upon transfer to lymphocyte-deficient Rag1-/- mice. Polarized Th1 cells downregulate IFN-γ and IL-2, and upregulate the negative regulatory receptor Tim-3, when treated with IFN-β in the absence of APCs. Further, IFN-β treatment of Th1 cells upregulates phosphorylation of Stat1, and downregulates phosphorylation of Stat4. Our data indicate that IFN-γ-producing Th1 cells are directly responsive to IFN-β and point to a novel mechanism of IFN-β-mediated T cell suppression that is independent of APC-derived signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Interferon-beta / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Th1 Cells / immunology*


  • Interferon-beta

Grant support

P.M.I.A.D. and A.P.R. are supported by funds from Université Laval. M.R. is supported by the EMD Serono, Canada and MS Research and Training Network Transitional Career Development Award from the MS Society of Canada and the Multiple Sclerosis Scientific Research Foundation; by a Junior-1 Research Scholar Career Award from the Fonds de Recherche Santé—Québec (FRQS); by a John R. Evans Leaders Fund Award from the Canada Foundation for Innovation (CFI); and by funds from the CHU de Québec—Université Laval. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.