Show simple item record

dc.contributor.authorMcKinstry, K. Kai
dc.contributor.authorAlam, Fahmida
dc.contributor.authorFlores-Malavet, Valeria
dc.contributor.authorNagy, Mate Z.
dc.contributor.authorSell, Stewart
dc.contributor.authorCooper, Andrea M.
dc.contributor.authorSwain, Susan L.
dc.contributor.authorStrutt, Tara M.
dc.date2022-08-11T08:09:54.000
dc.date.accessioned2022-08-23T16:47:57Z
dc.date.available2022-08-23T16:47:57Z
dc.date.issued2019-08-14
dc.date.submitted2019-09-19
dc.identifier.citation<p>PLoS Pathog. 2019 Aug 14;15(8):e1007989. doi: 10.1371/journal.ppat.1007989. eCollection 2019 Aug. <a href="https://doi.org/10.1371/journal.ppat.1007989">Link to article on publisher's site</a></p>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1007989
dc.identifier.pmid31412088
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41177
dc.description.abstractDefining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31412088&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright: © 2019 McKinstry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMemory T cells
dc.subjectT helper cells
dc.subjectInfluenza A virus
dc.subjectInflammation
dc.subjectNK cells
dc.subjectRespiratory infections
dc.subjectCytokines
dc.subjectT cells
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectPathological Conditions, Signs and Symptoms
dc.subjectPathology
dc.subjectVirus Diseases
dc.titleMemory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume15
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4981&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3965
dc.identifier.contextkey15377583
refterms.dateFOA2022-08-23T16:47:57Z
html.description.abstract<p>Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.</p>
dc.identifier.submissionpathoapubs/3965
dc.contributor.departmentDepartment of Pathology
dc.source.pagese1007989


Files in this item

Thumbnail
Name:
journal.ppat.1007989.pdf
Size:
2.381Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Copyright: © 2019 McKinstry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2019 McKinstry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.