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, ISSN: 1558-8238, Vol: 120, Issue: 12, Page: 4546-4557
2010
- 274Citations
- 133Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations274
- Citation Indexes274
- 274
- CrossRef244
- Captures133
- Readers133
- 133
Article Description
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-1Tim-3 HCV-specific CTLs greatly outnumbered PD-1Tim-3 CTLs in patients with acute resolving infection. Moreover, the population of PD-1Tim-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.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78649903057&origin=inward; http://dx.doi.org/10.1172/jci43127; http://www.ncbi.nlm.nih.gov/pubmed/21084749; http://www.jci.org/articles/view/43127#sd; http://dx.doi.org/10.1172/jci43127ds1; http://www.jci.org/articles/view/43127; https://dx.doi.org/10.1172/jci43127; https://www.jci.org/articles/view/43127
American Society for Clinical Investigation
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