CD25-targeted IL-2 signals promote improved outcomes of influenza infection and boost memory CD4 T cell formation
| Autor: | Susan L. Swain, Fahmida Alam, Andrea M. Cooper, Valeria Flores-Malavet, Stewart Sell, Ayushi Singh, K. Kai McKinstry, Tara M. Strutt |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_treatment T cell Immunology Biology medicine.disease_cause T-Lymphocytes Regulatory Article 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Orthomyxoviridae Infections In vivo Immunopathology medicine Influenza A virus Immunology and Allergy Animals IL-2 receptor Lung Inflammation Mice Inbred BALB C Interleukin-2 Receptor alpha Subunit Antibodies Monoclonal medicine.disease Up-Regulation Cytokine medicine.anatomical_structure Cytokines Interleukin-2 Female Cytokine storm Immunologic Memory 030215 immunology |
| Zdroj: | J Immunol |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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