Respiratory function following influenza A virus infection is improved with early CD25-targeted IL-2 administration 3575

Abstract Description Interleukin-2 is a pleotropic cytokine with potent pro- and anti-inflammatory effects. These divergent impacts can be directed in vivo by forming complexes of recombinant IL-2 and anti-IL-2 monoclonal antibodies (IL-2C) to target IL-2 to distinct subsets of cells based on their expression of subunits of the IL-2 receptor. Here, we show that administration of a prototypical anti-inflammatory IL-2C made with the JES6-1 anti-IL-2 antibody clone, which targets IL-2 to CD25+expressing cells at early phases of influenza A virus (IAV) infection, induces expansion of IAV-specific FR4+ CD73+ CTLA-4+ CD103+ CD25+ Foxp3+ regulatory CD4 T cells in the secondary lymphoid organs and lungs. However, anti-viral inflammatory responses on day 7 and clearance of virus from the lung are unimpeded in treated mice. Morbidity, measured by percent weight loss, and bronchial inflammation following IAV infection are, however, significantly reduced in mice with IL-2C treatment. In line with reduced bronchial inflammation, pulmonary function, measured by respiratory exchange and mid-tidal expiratory flow rates, is markedly improved during primary IAV infection in IL-2C treated versus untreated mice. Collectively, these observations support that CD25-targeted IL-2 administration has therapeutic potential to promote improved IAV infection outcomes that correlate with increased numbers of activated IAV-specific Foxp3+ CD4+ T regulatory cells. Funding Sources Supported by NIH/NIAID R01AI165406 Topic Categories Viral Immunology (VIR)