The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Negative Immune Regulator Tim-3 Is Overexpressed on T Cells in Hepatitis C Virus Infection and Its Blockade Rescues Dysfunctional CD4 + and CD8 + T Cells
Open accessAbstract
A number of emerging molecules and pathways have been implicated in mediating the T-cell exhaustion characteristic of chronic viral infection. Not all dysfunctional T cells express PD-1, nor are they all rescued by blockade of the PD-1/PD-1 ligand pathway. In this study, we characterize the expression of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) in chronic hepatitis C infection. For the first time, we found that Tim-3 expression is increased on CD4 + and CD8 + T cells in chronic hepatitis C virus (HCV) infection. The proportion of dually PD-1/Tim-3-expressing cells is greatest in liver-resident T cells, significantly more so in HCV-specific than in cytomegalovirus-specific cytotoxic T lymphocytes. Tim-3 expression correlates with a dysfunctional and senescent phenotype (CD127 low CD57 high ), a central rather than effector memory profile (CD45RA negative CCR7 high ), and reduced Th1/Tc1 cytokine production. We also demonstrate the ability to enhance T-cell proliferation and gamma interferon production in response to HCV-specific antigens by blocking the Tim-3-Tim-3 ligand interaction. These findings have implications for the development of novel immunotherapeutic approaches to this common viral infection.
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Cites
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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Global epidemiology of hepatitis C virus infection
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The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
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Self-citationMemory CD8+ T cells vary in differentiation phenotype in different persistent virus infections
Appay, V., Dunbar, P. R., Callan, M., Klenerman, P., Gillespie, G. M. A., Papagno, L., Ogg, G. S., King, A., Lechner, F., Spina, C. A., et al. (2002) · Nature Medicine · doi:10.1038/nm0402-379 · Cited by 1,571
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Sustained Dysfunction of Antiviral CD8+T Lymphocytes after Infection with Hepatitis C Virus
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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
Self-citationTargeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
Self-citationFourcade, J., Sun, Z., Benallaoua, M., Guillaume, P., Luescher, I. F., Sander, C., Kirkwood, J. M., Kuchroo, V., & Zarour, H. M. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100637 · Cited by 1,307
Self-citationTIM3 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
Self-citationTim‐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
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Metadata
- Authors
- Golden-Mason, L., Palmer, B. E., Kassam, N., Townshend-Bulson, L., Livingston, S., McMahon, B. J., Castelblanco, N., Kuchroo, V., Gretch, D. R., & Rosen, H. R.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2009-09-15
- Volume
- 83
- Issue
- 18
- Pages
- 9122-9130
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2168231169
- Cited by
- 431
- References
- 25
- FWCI
- 22.08
- Type
- journal article
- Language
- en
- Open access
- green
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- Golden-Mason, L., Palmer, B. E., Kassam, N., Townshend-Bulson, L., Livingston, S., McMahon, B. J., Castelblanco, N., Kuchroo, V., Gretch, D. R., & Rosen, H. R. (2009). Negative Immune Regulator Tim-3 Is Overexpressed on T Cells in Hepatitis C Virus Infection and Its Blockade Rescues Dysfunctional CD4 + and CD8 + T Cells. Journal of Virology. https://doi.org/10.1128/jvi.00639-09
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
