CD25-Targeted IL-2 Signals Promote Improved Outcomes of Influenza Infection and Boost Memory CD4 T Cell Formation

J Immunol. 2020 Jun 15;204(12):3307-3314. doi: 10.4049/jimmunol.2000205. Epub 2020 May 6.


IL-2 is a pleotropic cytokine with potent pro- and anti-inflammatory effects. These divergent impacts can be directed in vivo by forming complexes of IL-2 and anti-IL-2 mAbs (IL-2C) to target IL-2 to distinct subsets of cells based on their expression of subunits of the IL-2R. In this study, we show that treatment of mice with a prototypical anti-inflammatory IL-2C, JES6-1-IL-2C, best known to induce CD25+ regulatory CD4 T cell expansion, surprisingly causes robust induction of a suite of inflammatory factors. However, treating mice infected with influenza A virus with this IL-2C reduces lung immunopathology. We compare the spectrum of inflammatory proteins upregulated by pro- and anti-inflammatory IL-2C treatment and uncover a pattern of expression that reveals potentially beneficial versus detrimental aspects of the influenza-associated cytokine storm. Moreover, we show that anti-inflammatory IL-2C can deliver survival signals to CD4 T cells responding to influenza A virus that improve their memory fitness, indicating a novel application of IL-2 to boost pathogen-specific T cell memory while simultaneously reducing immunopathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / immunology
  • Female
  • Immunologic Memory / immunology*
  • Inflammation / immunology
  • Inflammation / virology
  • Influenza A virus / immunology*
  • Interleukin-2 / immunology*
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Lung / immunology
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Up-Regulation / immunology


  • Antibodies, Monoclonal
  • Cytokines
  • Il2ra protein, mouse
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit