The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity
Open accessAbstract
Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%-80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1-Tim-3- HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches.
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Cites
Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection
Fried, M. W., Shiffman, M. L., Reddy, K. R., Smith, C., Marinos, G., Gonçales, F. L., Häussinger, D., Diago, M., Carosi, G., Dhumeaux, D., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020047 · Cited by 6,389
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 1×
“Differentiation of T cells into effector cells during primary immune responses has important consequences for the development of protective immunity, and taken together, our results indicate that PD-1 and Tim-3 coexpression demarcates a TCM phenotypic signature with limited functional capacities (29) that favor establ…”
ResultRestoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2006) · Nature · doi:10.1038/nature04444 · Cited by 3,986
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Help for cytotoxic-T-cell responses is mediated by CD40 signalling
Bennett, S. R. M., Carbone, F. R., Karamalis, F., Flavell, R. A., Miller, J. F. A. P., & Heath, W. R. (1998) · Nature · doi:10.1038/30996 · Cited by 2,092
Effector and memory T-cell differentiation: implications for vaccine development
Kaech, S. M., Wherry, E. J., & Ahmed, R. (2002) · Nature Reviews Immunology · doi:10.1038/nri778 · Cited by 1,865 · cited 1×
“Provision of adequate CD4+ T cell help via production of cytokines (41) or by assisting professional antigen-presenting cells via CD40/CD40L-mediated activation (42, 43) is a prerequisite for the generation of effective CTL memory and development of protective immunity to HCV.”
BackgroundHIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
Betts, M. R. (2006) · Blood · doi:10.1182/blood-2005-12-4818 · Cited by 1,826
Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R., & Ahmed, R. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4911-4927.2003 · Cited by 1,610
Monney, L., Sabatos, C. A., Gaglia, J. L., Ryu, A., Waldner, H., Chernova, T., Manning, S., Greenfield, E. A., Coyle, A. J., Sobel, R. A., et al. (2002) · Nature · doi:10.1038/415536a · Cited by 1,472
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,354
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
Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients
Baitsch, L., Baumgaertner, P., Devêvre, E., Raghav, S. K., Legat, A., Barba, L., Wieckowski, S., Bouzourene, H., Deplancke, B., Romero, P., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46102 · Cited by 845
Li, H., Wu, K., Tao, K., Chen, L., Zheng, Q., Lu, X., Liu, J., Shi, L., Liu, C., Wang, G., et al. (2012) · Hepatology · doi:10.1002/hep.25777 · Cited by 496
CD8+ T Cell Exhaustion in Cancer
Dolina, J. S., Van Braeckel-Budimir, N., Thomas, G. D., & Salek-Ardakani, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.715234 · Cited by 489
Metadata
- Authors
- McMahan, R. H., Golden-Mason, L., Nishimura, M. I., McMahon, B. J., Kemper, M., Allen, T. M., Gretch, D. R., & Rosen, H. R.
- Venue
- Journal of Clinical Investigation
- Published
- 2010-12-01
- Volume
- 120
- Issue
- 12
- Pages
- 4546-4557
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2144373841
- Cited by
- 305
- References
- 47
- FWCI
- 16.37
- Type
- journal article
- Language
- en
- Open access
- bronze
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- McMahan, R. H., Golden-Mason, L., Nishimura, M. I., McMahon, B. J., Kemper, M., Allen, T. M., Gretch, D. R., & Rosen, H. R. (2010). Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. Journal of Clinical Investigation. https://doi.org/10.1172/jci43127
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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