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| Status |
Public on Feb 09, 2021 |
| Title |
Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Hepatitis B virus-specific (HBV-specific) CD8+ T cells fail to acquire effector functions after priming in the liver, but the molecular basis for the dysfunction is poorly understood. By comparing the gene expression profile of intrahepatically primed, dysfunctional HBV-specific CD8+ T cells with that of systemically primed, functional effector counterparts, we found that the expression of interferon-stimulated genes (ISGs) is selectively suppressed in the dysfunctional CD8+ T cells. The ISG suppression was associated with impaired phosphorylation of STAT1 in response to IFN-α treatment. Importantly, a strong induction of type I interferons (IFN-Is) in the liver facilitated the functional differentiation of intrahepatically primed HBV-specific CD8+ T cells in association with the restoration of ISGs' expression in the T cells. These results suggest that intrahepatic priming suppresses IFN-I signaling in CD8+ T cells, which may contribute to the dysfunction. The data also suggest a therapeutic value of the robust induction of intrahepatic IFN-Is for the treatment of chronic HBV infection.
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| Overall design |
We compared the gene expression profile between naïve, dysfunctional and effector HBV-specific CD8+ T cells by using microarray .Specifically, HBcAg derived peptide (COR93)-specific CD8+ T cells were adoptively transferred into HBV-Tg mice (lineage 1.3.32, inbred B6, H-2b) to obtain tolerant COR93-specific T cells. To obtain effector COR93-specific T cells, we adoptively transferred the same T cells into B6 mice treated with an agonistic anti-CD40 antibody and COR93 peptide . Seven days later, adoptively transferred COR93-specific CD8+ T cells were purified from Intrahepatic lymphocytes of HBV-Tg mice. Donor naïve COR93-specific CD8 T cells were also purified for comparison.
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| Web link |
https://doi.org/10.1172/jci.insight.145761
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| Contributor(s) |
Kawashima K, Isogawa M, Onishi M |
| Citation(s) |
33400688 |
| Submission date |
Oct 21, 2020 |
| Last update date |
Feb 12, 2021 |
| Contact name |
masaya onishi |
| E-mail(s) |
om19840905@gmail.com
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| Phone |
+81-52-853-8191
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| Organization name |
Nagoya City University Graduate School of Medical Sciences
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| Department |
Virology & Liver unit
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| Street address |
Kawasumi, Mizuho
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| City |
Nagoya |
| ZIP/Postal code |
467-8601 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA670407 |
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