tetano
Editor, Senior Moderator
J Immunol. 2020 May 6. pii: ji2000205. doi: 10.4049/jimmunol.2000205. [Epub ahead of print]
CD25-Targeted IL-2 Signals Promote Improved Outcomes of Influenza Infection and Boost Memory CD4 T Cell Formation.
Alam F[SUP]1[/SUP], Singh A[SUP]1[/SUP], Flores-Malavet V[SUP]1[/SUP], Sell S[SUP]2[/SUP], Cooper AM[SUP]3[/SUP], Swain SL[SUP]4[/SUP], McKinstry KK[SUP]1,[/SUP][SUP]5[/SUP], Strutt TM[SUP]6,[/SUP][SUP]5[/SUP].
Author information
Abstract
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[SUP]+[/SUP] 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.
Copyright ? 2020 by The American Association of Immunologists, Inc.
PMID:32376651DOI:10.4049/jimmunol.2000205
CD25-Targeted IL-2 Signals Promote Improved Outcomes of Influenza Infection and Boost Memory CD4 T Cell Formation.
Alam F[SUP]1[/SUP], Singh A[SUP]1[/SUP], Flores-Malavet V[SUP]1[/SUP], Sell S[SUP]2[/SUP], Cooper AM[SUP]3[/SUP], Swain SL[SUP]4[/SUP], McKinstry KK[SUP]1,[/SUP][SUP]5[/SUP], Strutt TM[SUP]6,[/SUP][SUP]5[/SUP].
Author information
Abstract
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[SUP]+[/SUP] 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.
Copyright ? 2020 by The American Association of Immunologists, Inc.
PMID:32376651DOI:10.4049/jimmunol.2000205