Spatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4+ T cells

Nat Immunol. 2020 Mar;21(3):321-330. doi: 10.1038/s41590-020-0596-6. Epub 2020 Feb 17.


Differentiation of CD4+ T cells into either follicular helper T (TFH) or type 1 helper T (TH1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here we analyzed the spatiotemporal dynamics of CD4+ T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies, or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced production of the cytokine IL-6 and drove TFH cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into TH1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4+ T cell differentiation and might instruct vaccine design strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Female
  • Interferon Type I / metabolism*
  • Interleukin-6 / biosynthesis
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spatio-Temporal Analysis
  • T-Lymphocytes, Helper-Inducer / immunology
  • Th1 Cells / immunology
  • Vesicular stomatitis Indiana virus / immunology
  • Vesicular stomatitis Indiana virus / pathogenicity
  • Vesicular stomatitis New Jersey virus / immunology
  • Vesicular stomatitis New Jersey virus / pathogenicity


  • Interferon Type I
  • Interleukin-6
  • interleukin-6, mouse