Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus
Tissue-resident memory T (TRM) cells provide first-line defense against invading pathogens encountered at barrier sites. In the lungs, TRM cells protect against respiratory infections, but wane more quickly than TRM cells in other tissues. This lack of a sustained TRM population in the lung parenchy...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01861/full |
| _version_ | 1828786901769781248 |
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| author | Kaitlyn M. Morabito Kaitlyn M. Morabito Tracy J. Ruckwardt Erez Bar-Haim Erez Bar-Haim Deepika Nair Syed M. Moin Alec J. Redwood David A. Price David A. Price Barney S. Graham |
| author_facet | Kaitlyn M. Morabito Kaitlyn M. Morabito Tracy J. Ruckwardt Erez Bar-Haim Erez Bar-Haim Deepika Nair Syed M. Moin Alec J. Redwood David A. Price David A. Price Barney S. Graham |
| author_sort | Kaitlyn M. Morabito |
| collection | DOAJ |
| description | Tissue-resident memory T (TRM) cells provide first-line defense against invading pathogens encountered at barrier sites. In the lungs, TRM cells protect against respiratory infections, but wane more quickly than TRM cells in other tissues. This lack of a sustained TRM population in the lung parenchyma explains, at least in part, why infections with some pathogens, such as influenza virus and respiratory syncytial virus (RSV), recur throughout life. Intranasal (IN) vaccination with a murine cytomegalovirus (MCMV) vector expressing the M protein of RSV (MCMV-M) has been shown to elicit robust populations of CD8+ TRM cells that accumulate over time and mediate early viral clearance. To extend this finding, we compared the inflationary CD8+ T cell population elicited by MCMV-M vaccination with a conventional CD8+ T cell population elicited by an MCMV vector expressing the M2 protein of RSV (MCMV-M2). Vaccination with MCMV-M2 induced a population of M2-specific CD8+ TRM cells that waned rapidly, akin to the M2-specific CD8+ TRM cell population elicited by infection with RSV. In contrast to the natural immunodominance profile, however, coadministration of MCMV-M and MCMV-M2 did not suppress the M-specific CD8+ T cell response, suggesting that progressive expansion was driven by continuous antigen presentation, irrespective of the competitive or regulatory effects of M2-specific CD8+ T cells. Moreover, effective viral clearance mediated by M-specific CD8+ TRM cells was not affected by the coinduction of M2-specific CD8+ T cells. These data show that memory inflation is required for the maintenance of CD8+ TRM cells in the lungs after IN vaccination with MCMV. |
| first_indexed | 2024-12-12T00:19:45Z |
| format | Article |
| id | doaj.art-c945c838557b41e79f92598e2bdcbe96 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T00:19:45Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c945c838557b41e79f92598e2bdcbe962022-12-22T00:44:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01861378605Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine CytomegalovirusKaitlyn M. Morabito0Kaitlyn M. Morabito1Tracy J. Ruckwardt2Erez Bar-Haim3Erez Bar-Haim4Deepika Nair5Syed M. Moin6Alec J. Redwood7David A. Price8David A. Price9Barney S. Graham10Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, United StatesViral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesViral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, IsraelViral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesViral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesInstitute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, AustraliaDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United KingdomHuman Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesViral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesTissue-resident memory T (TRM) cells provide first-line defense against invading pathogens encountered at barrier sites. In the lungs, TRM cells protect against respiratory infections, but wane more quickly than TRM cells in other tissues. This lack of a sustained TRM population in the lung parenchyma explains, at least in part, why infections with some pathogens, such as influenza virus and respiratory syncytial virus (RSV), recur throughout life. Intranasal (IN) vaccination with a murine cytomegalovirus (MCMV) vector expressing the M protein of RSV (MCMV-M) has been shown to elicit robust populations of CD8+ TRM cells that accumulate over time and mediate early viral clearance. To extend this finding, we compared the inflationary CD8+ T cell population elicited by MCMV-M vaccination with a conventional CD8+ T cell population elicited by an MCMV vector expressing the M2 protein of RSV (MCMV-M2). Vaccination with MCMV-M2 induced a population of M2-specific CD8+ TRM cells that waned rapidly, akin to the M2-specific CD8+ TRM cell population elicited by infection with RSV. In contrast to the natural immunodominance profile, however, coadministration of MCMV-M and MCMV-M2 did not suppress the M-specific CD8+ T cell response, suggesting that progressive expansion was driven by continuous antigen presentation, irrespective of the competitive or regulatory effects of M2-specific CD8+ T cells. Moreover, effective viral clearance mediated by M-specific CD8+ TRM cells was not affected by the coinduction of M2-specific CD8+ T cells. These data show that memory inflation is required for the maintenance of CD8+ TRM cells in the lungs after IN vaccination with MCMV.https://www.frontiersin.org/article/10.3389/fimmu.2018.01861/fullCD8+ T cellscytomegalovirusmemory inflationrespiratory syncytial virustissue-resident memoryvaccine |
| spellingShingle | Kaitlyn M. Morabito Kaitlyn M. Morabito Tracy J. Ruckwardt Erez Bar-Haim Erez Bar-Haim Deepika Nair Syed M. Moin Alec J. Redwood David A. Price David A. Price Barney S. Graham Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus Frontiers in Immunology CD8+ T cells cytomegalovirus memory inflation respiratory syncytial virus tissue-resident memory vaccine |
| title | Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus |
| title_full | Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus |
| title_fullStr | Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus |
| title_full_unstemmed | Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus |
| title_short | Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus |
| title_sort | memory inflation drives tissue resident memory cd8 t cell maintenance in the lung after intranasal vaccination with murine cytomegalovirus |
| topic | CD8+ T cells cytomegalovirus memory inflation respiratory syncytial virus tissue-resident memory vaccine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01861/full |
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