Memory regulatory T cells home to the lung and control influenza A virus infection
- 22 May 2019
- journal article
- research article
- Published by Wiley in Immunology & Cell Biology
- Vol. 97 (9), 774-786
- https://doi.org/10.1111/imcb.12271
Abstract
Memory regulatory T cells (mTregs) have been demonstrated to persist long‐term in hosts after the resolution of primary influenza A virus (IAV) infection. However, whether such IAV infection‐experienced (IAV‐experienced) mTregs differentiate into a phenotypically and functionally distinct Treg subset and what function they play at the infection site remain poorly defined. In this study, we characterized the phenotype, examined the responsiveness and assessed the suppressive function of IAV‐experienced mTregs. In comparison with inexperienced naïve Tregs (nTregs), mTregs exhibited elevated expression of CD39, CD69, CD103, CTLA‐4, LFA‐1 and PD‐1 and could be activated in an antigen‐specific manner in vitro and in vivo. When mTregs and nTregs were adoptively co‐transferred into recipient mice, mTregs had a competitive advantage in migrating to the IAV infected lungs. mTregs were more capable of controlling in vitro proliferation of CD4+ and CD8+ T cells and suppressed CD40 and CD86 upregulation on bone marrow‐derived dendritic cells (BMDCs). Adoptively transferred mTregs, but not nTregs, significantly attenuated body weight loss, lung pathology and immune cell infiltration into the infected lungs. These results suggest that mTregs generated after IAV infection differentiate into a phenotypically distinct and functionally enhanced Treg subset that can be activated in an antigen‐specific manner to exert immunosuppression. We propose vaccination to induce such mTregs as a potential novel strategy to protect against severe IAV infection.Keywords
Funding Information
- National Health and Medical Research Council (603104, 567122)
This publication has 44 references indexed in Scilit:
- Viral Antigen Induces Differentiation of Foxp3+ Natural Regulatory T Cells in Influenza Virus–Infected MiceThe Journal of Immunology, 2013
- Influenza A Virus Infection Results in a Robust, Antigen-Responsive, and Widely Disseminated Foxp3 + Regulatory T Cell ResponseJournal of Virology, 2012
- Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus InfectionCell, 2011
- Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient MiceJournal of Virology, 2010
- CD25 + Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus InfectionJournal of Virology, 2010
- Foxp3+ CD4 Regulatory T Cells Limit Pulmonary Immunopathology by Modulating the CD8 T Cell Response during Respiratory Syncytial Virus InfectionPublished by The American Association of Immunologists ,2010
- CD39+Foxp3+ Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple SclerosisPublished by The American Association of Immunologists ,2009
- Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungsThe Journal of Experimental Medicine, 2008
- Coordination of Early Protective Immunity to Viral Infection by Regulatory T CellsScience, 2008
- Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3Immunity, 2005