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Cited by 186Hepatitis B Virus StudiesT-cell and B-cell ImmunologyLiver physiology and pathology

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Oscillating CD8+ T Cell Effector Functions after Antigen Recognition in the Liver

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Isogawa, Masanori, Furuichi, Yoshihiro, Chisari, Francis V.·2005·Immunity
DOI 10.1016/j.immuni.2005.05.005
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Abstract

When hepatitis B virus (HBV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) are adoptively transferred into HBV transgenic mice, they enter the liver, recognize antigen, secrete interferon gamma (IFNgamma), inhibit viral replication, and kill their target cells, causing hepatitis. In the current study, we examined the impact of antigen recognition on the evolution of the activation phenotype, antiviral effector functions, expansion and contraction kinetics, and compartmentalization of the transferred CTLs. The results reveal that noncytolytic and cytolytic effector functions and expansion-contraction kinetics of the CTLs are regulated asynchronously and in an oscillatory manner as a consequence of antigen recognition in the liver and in association with PD-1 upregulation. We suggest that such oscillations maximize viral clearance and minimize tissue injury during HBV infection and that poor coordination of these events could lead to viral persistence and chronic liver disease.

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Metadata

Authors
Isogawa, M., Furuichi, Y., & Chisari, F. V.
Affiliations
Scripps Research Institute (US)
Corresponding author
Chisari, Francis V.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2005-07
Volume
23
Issue
1
Pages
53-63
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2005.05.005
OpenAlex
W2047908014
Cited by
186
References
0
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 11 · 2012: 11
FWCI
10.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA40489)
Topics
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
hepatitis B virus, CD8+ cytotoxic T lymphocytes, antigen recognition, PD-1, interferon-gamma, viral clearance, liver, chronic hepatitis B, viral persistence, chronic liver disease, HBV transgenic mice
MeSH terms
Animals, Hepatitis B, Hepatitis B Surface Antigens, Immunologic Memory, Interferon-gamma, Liver, Mice, Transgenic, Receptors, Antigen, T-Cell, Serine Endopeptidases, Spleen, T-Lymphocytes, Cytotoxic, Viral Envelope Proteins, Adoptive Transfer, Mice, Granzymes

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