The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Upregulation of the Tim-3/Galectin-9 Pathway of T Cell Exhaustion in Chronic Hepatitis B Virus Infection
Open accessAbstract
The S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T cells and induces their apoptotic deletion or functional inactivation. We investigated whether galectin-9/Tim-3 interactions contribute to the deletion and exhaustion of the antiviral T cell response in chronic hepatitis B virus infection (CHB). We found Tim-3 to be expressed on a higher percentage of CD4 and CD8 T cells from patients with CHB than healthy controls (p<0.0001) and to be enriched on activated T cells and those infiltrating the HBV-infected liver. Direct ex vivo examination of virus-specific CD8 T cells binding HLA-A2/peptide multimers revealed that Tim-3 was more highly upregulated on HBV-specific CD8 T cells than CMV-specific CD8 T cells or the global CD8 T cell population in patients with CHB (p<0.001) or than on HBV-specific CD8 after resolution of infection. T cells expressing Tim-3 had an impaired ability to produce IFN-γ and TNF-α upon recognition of HBV-peptides and were susceptible to galectin-9-triggered cell death in vitro. Galectin-9 was detectable at increased concentrations in the sera of patients with active CHB-related liver inflammation (p = 0.02) and was strongly expressed by Kupffer cells within the liver sinusoidal network. Tim-3 blockade resulted in enhanced expansion of HBV-specific CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. Blocking PD-1 in combination with Tim-3 enhanced the number of patients from whom functional antiviral responses could be recovered and/or the strength of responses, indicating that these co-inhibitory molecules play a non-redundant role in driving T cell exhaustion in CHB. Patients taking antivirals able to potently suppress HBV viraemia continued to express Tim-3 on their T cells and respond to Tim-3 blockade. In summary, both Tim-3 and galectin-9 are increased in CHB and may contribute to the inhibition and deletion of T cells as they infiltrate the HBV-infected liver.
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The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
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EASL clinical practice guidelines management of chronic hepatitis B
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EASL Clinical Practice Guidelines: Management of chronic hepatitis B
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Intracellular Inactivation of the Hepatitis B Virus by Cytotoxic T Lymphocytes
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Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection
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Turning 'sweet' on immunity: galectin–glycan interactions in immune tolerance and inflammation
Rabinovich, G. A., & Toscano, M. A. (2009) · Nature Reviews Immunology · doi:10.1038/nri2536 · Cited by 904
Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection
Jin, H.-T., Anderson, A. C., Tan, W. G., West, E. E., Ha, S.-J., Araki, K., Freeman, G. J., Kuchroo, V. K., & Ahmed, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009731107 · Cited by 858
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Cited by
Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.001 · Cited by 2,096
TIM3 comes of age as an inhibitory receptor
Wolf, Y., Anderson, A. C., & Kuchroo, V. K. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0224-6 · Cited by 959
Tim‐3 and its role in regulating anti‐tumor immunity
Das, M., Zhu, C., & Kuchroo, V. K. (2017) · Immunological Reviews · doi:10.1111/imr.12520 · Cited by 856
Ju, C., & Tacke, F. (2016) · Cellular & Molecular Immunology · doi:10.1038/cmi.2015.104 · Cited by 554
A global scientific strategy to cure hepatitis B
Revill, P. A., Chisari, F. V., Block, J. M., Dandri, M., Gehring, A. J., Guo, H., Hu, J., Kramvis, A., Lampertico, P., Janssen, H. L. A., et al. (2019) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30119-0 · Cited by 508
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Metadata
- Authors
- Nebbia, G., Peppa, D., Schurich, A., Khanna, P., Singh, H. D., Cheng, Y., Rosenberg, W., Dusheiko, G., Gilson, R., ChinAleong, J., Kennedy, P., & Maini, M. K.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-10-24
- Volume
- 7
- Issue
- 10
- Pages
- e47648
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2046828081
- Cited by
- 276
- References
- 27
- FWCI
- 12.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- Nebbia, G., Peppa, D., Schurich, A., Khanna, P., Singh, H. D., Cheng, Y., Rosenberg, W., Dusheiko, G., Gilson, R., ChinAleong, J., Kennedy, P., & Maini, M. K. (2012). Upregulation of the Tim-3/Galectin-9 Pathway of T Cell Exhaustion in Chronic Hepatitis B Virus Infection. PLoS ONE. https://doi.org/10.1371/journal.pone.0047648
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