Healthy but not RSV-infected lung epithelial cells profoundly inhibit T cell activation
Open accessAbstract
BACKGROUND: Respiratory viruses, including respiratory syncytial virus (RSV), can cause asthma exacerbations and bronchiolitis. Both conditions are associated with enhanced cognate immune responses and inflammation and reduced immune regulation. Lung epithelial cells (LECs) can contribute to antiviral and allergic immune responses while gut epithelial cells can inhibit effector T cell responses. A study was performed to determine whether healthy LECs regulate antigen-specific T cell responses and if this regulation is lost during RSV infection. METHODS: LA4 cells, a murine LEC line, infected with RSV or primary murine LECs were co-cultured with ovalbumin-specific T cell receptor transgenic CD4+ T cells from DO11.10 mice and ovalbumin-pulsed bone marrow-derived dendritic cells (DC) to assess T cell proliferation by flow cytometry and cytokine production. RESULTS: The presence of LECs abrogated DC-induced T cell proliferation and significantly reduced T cell cytokine release. These effects of LECs were predominantly contact-dependent, primarily affected T cells directly and were partly mediated by transforming growth factor beta. Soluble factors and DC-mediated effects also contributed to T cell inhibition. RSV infection of LECs reduced their inhibitory capacity in an infection dose-dependent manner. This was independent of proinflammatory cytokines released by infected LECs, but in part due to Toll-like receptor activation and to infection-induced cell death. CONCLUSION: Healthy LECs are potent inhibitors of T cell activation, but this regulatory function is lost after RSV infection. These findings suggest a central role for LECs in maintaining the tolerogenic environment of healthy lungs. Loss of this regulatory capacity after viral infection may allow development of excessive cognate immune responses and pulmonary inflammation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Rhinovirus binds MDA5 to inhibit its activity.
“For instance, influenza virus (91) and RSV (161) bind RIG-I and rhinovirus binds MDA5 to inhibit their activity (304)”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [304]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955 · see citing works
Community study of role of viral infections in exacerbations of asthma in 9–11 year old children
Johnston, S. L., Pattemore, P. K., Sanderson, G., Smith, S., Lampe, F., Josephs, L., Symington, P., Toole, S. O., Myint, S. H., Tyrrell, D. A. J., et al. (1995) · BMJ · doi:10.1136/bmj.310.6989.1225 · Cited by 1,991 · see citing works
Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus
Kurt-Jones, E., Popova, L., Kwinn, L. A., Haynes, L., Jones, L. P., Tripp, R., Walsh, E., Freeman, M., Golenbock, D., Anderson, L., et al. (2000) · Nature Immunology · doi:10.1038/80833 · Cited by 1,842 · see citing works
Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years
Stein, R. T., Sherrill, D. L., Morgan, W. J., Holberg, C. J., Halonen, M. J., Taussig, L. M., Wright, A. L., & Martínez, F. D. (1999) · The Lancet · doi:10.1016/s0140-6736(98)10321-5 · Cited by 1,628 · see citing works
Nakamura, K., Kitani, A., & Strober, W. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.5.629 · Cited by 1,596 · see citing works
Type I Interferons in Host Defense
Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.007 · Cited by 1,194 · see citing works
Mechanisms of suppression by suppressor T cells
von Boehmer, H. (2005) · Nature Immunology · doi:10.1038/ni1180 · Cited by 1,005 · see citing works
Severe Respiratory Syncytial Virus Bronchiolitis in Infancy and Asthma and Allergy at Age 13
Sigurs, N., Gustafsson, P., Bjarnason, R. G., Lundberg, F., Schmidt, S., Sigurbergsson, F., & Kjellman, B. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200406-730oc · Cited by 954 · see citing works
Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., et al. (2003) · Nature · doi:10.1038/nature01850 · Cited by 847 · see citing works
Foxp3 in control of the regulatory T cell lineage
Zheng, Y., & Rudensky, A. Y. (2007) · Nature Immunology · doi:10.1038/ni1455 · Cited by 699 · see citing works
Smyth, R. L., & Openshaw, P. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69077-6 · Cited by 635 · see citing works
Respiratory syncytial virus infection
Simões, E. A. F. (1999) · The Lancet · doi:10.1016/s0140-6736(99)80040-3 · Cited by 603 · see citing works
PD-1 and its ligands in T-cell immunity
Keir, M. E., Francisco, L. M., & Sharpe, A. H. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.012 · Cited by 432 · see citing works
Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma
Wark, P. A. B., Johnston, S. L., Morić, I., Simpson, J. L., Hensley, M. J., & Gibson, P. G. (2001) · European Respiratory Journal · doi:10.1183/09031936.02.00226302 · Cited by 372 · see citing works
Taking our breath away: dendritic cells in the pathogenesis of asthma
Lambrecht, B. N., & Hammad, H. (2003) · Nature reviews. Immunology · doi:10.1038/nri1249 · Cited by 341 · see citing works
DO11.10 and OT-II T Cells Recognize a C-Terminal Ovalbumin 323–339 Epitope
Robertson, J. M., Jensen, P. E., & Evavold, B. D. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4706 · Cited by 332 · see citing works
Isolation and Primary Culture of Murine Alveolar Type II Cells
Corti, M., Brody, A. R., & Harrison, J. H. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.14.4.8600933 · Cited by 320 · see citing works
Glycosaminoglycan Sulfation Requirements for Respiratory Syncytial Virus Infection
Hallak, L. K., Spillmann, D., Collins, P. L., & Peeples, M. E. (2000) · Journal of Virology · doi:10.1128/jvi.74.22.10508-10513.2000 · Cited by 311 · see citing works
The regulation of allergy and asthma
Umetsu, D. T., & DeKruyff, R. H. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00413.x · Cited by 266 · see citing works
Differential Response of Dendritic Cells to Human Metapneumovirus and Respiratory Syncytial Virus
Guerrero-Plata, A., Casola, A., Suárez, G., Yu, X., Spetch, L., Peeples, M. E., & Garofalo, R. P. (2005) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0287oc · Cited by 193 · see citing works
Yehualaeshet, T., O'Connor, R. N., Green-Johnson, J. M., Mai, S., Silverstein, R. L., Murphy-Ullrich, J. E., & Khalil, N. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65183-8 · Cited by 180 · see citing works
Brimnes, M. K., Bonifaz, L. C., Steinman, R. M., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030266 · Cited by 165 · see citing works
Transforming Growth Factor-β1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease
Alcorn, J. F., Rinaldi, L. M., Jaffe, E. F., van Loon, M., Bates, J. H. T., Janssen-Heininger, Y. M. W., & Irvin, C. G. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200702-334oc · Cited by 117 · see citing works
Beyer, M., Bartz, H., Hörner, K., Doths, S., Koerner‐Rettberg, C., & Schwarze, J. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2003.10.057 · Cited by 109 · see citing works
Self-citationControls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection
Grayson, M. H., Ramos, M. S., Rohlfing, M. M., Kitchens, R. T., Wang, H. D., Gould, A. P., Agapov, E. V., & Holtzman, M. J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1438 · Cited by 101 · see citing works
Self-citationStanciu, L. A., Bellettato, C. M., Laza‐Stanca, V., Coyle, A. J., Papi, A. A., & Johnston, S. L. (2006) · The Journal of Infectious Diseases · doi:10.1086/499275 · Cited by 99 · see citing works
Garrigan, K., Rawson, P. M., McMurray, C., Hermans, I. F., Abernethy, N., Watson, J., & Ronchese, F. (1996) · Blood · doi:10.1182/blood.v88.9.3508.bloodjournal8893508 · Cited by 95 · see citing works
IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells
Temann, U.-A., Laouar, Y., Eynon, E. E., Homer, R., & Flavell, R. A. (2006) · International Immunology · doi:10.1093/intimm/dxl117 · Cited by 86 · see citing works
Clonal isolation of epithelial cells from mouse lung adenoma.
Stoner, G. D., Kikkawa, Y., Kniazeff, A. J., et al. (1975) · PubMed · Cited by 58 · see citing works
Colonic epithelial cell mediated suppression of CD4 T cell activation
Cruickshank, S. M., McVay, L. D., Baumgart, D. C., et al. (2004) · Gut · doi:10.1136/gut.2003.029967 · Cited by 55 · see citing works
Wang, H., Peters, N., Laza‐Stanca, V., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2536 · Cited by 50 · see citing works
Self-citationMak, T. W., & Saunders, M. E. (2006) · Elsevier eBooks · doi:10.1016/b978-012088451-3.50016-8 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Barrier Epithelial Cells and the Control of Type 2 Immunity
Hammad, H., & Lambrecht, B. N. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.007 · Cited by 847 · see citing works
The airway epithelium: soldier in the fight against respiratory viruses
Vareille, M., Kieninger, E., Edwards, M. R., & Regamey, N. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-10 · Cited by 655 · see citing works
- Authors
- Wang, H., Su, Z., & Schwarze, J.
- Affiliations
- Centre for Inflammation Research (GB)
- Jiangsu Province Hospital (CN)
- Corresponding author
- Schwarze, J
- ORCID
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2009-01-08
- Volume
- 64
- Issue
- 4
- Pages
- 283-290
- ISSN
- 0040-6376 (ISSN-L)
- PMC
- PMC2655656
- OpenAlex
- W2160852691
- Cited by
- 39
- References
- 32
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Thorax (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust (067454, ID 067454)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- respiratory syncytial virus, lung epithelial cells, T cell activation, T cell suppression, dendritic cells, ovalbumin-specific T cells, TGF-beta, Toll-like receptor activation, asthma exacerbations, bronchiolitis, lung inflammation
- MeSH terms
- Analysis of Variance, Animals, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Female, Flow Cytometry, Immunity, Cellular, Lymphocyte Activation, Mice, Inbred BALB C, Pneumonia, Viral, Pulmonary Alveoli, T-Lymphocytes, Cytokines, Respiratory Syncytial Virus Infections, Cell Proliferation, Toll-Like Receptors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
