The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Memory CD8 + T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection
Open accessAbstract
Few hepatitis C virus (HCV) infections resolve spontaneously but those that do appear to afford protective immunity. Second infections are usually shorter in duration and are less likely to persist but mechanisms of virus control in immune individuals have not been identified. In this study we investigated whether memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees serially reinfected with the virus. Clearance of the first infection took 3–4 mo and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High frequencies of memory T cells targeting multiple HCV proteins were stable over 7 yr of follow-up. Animals were infected for a second time to assess the protective role of memory T cells. In contrast to the prolonged course of the first infection, viremia was terminated within 14 d. Control of this second infection was kinetically linked to rapid acquisition of virus-specific cytolytic activity by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in blood. The importance of memory CD8+ T cells in control of HCV infection was confirmed by antibody-mediated depletion of this lymphocyte subset before a third infection. Virus replication was prolonged despite the presence of memory CD4+ T helper cells primed by the two prior infections and was not terminated until HCV-specific CD8+ T cells recovered in the liver. These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A central role for CD8+ CTLs in virus elimination in the liver is supported by experimental depletion studies in which depletion of CD8+ T cells delays clearance of hepatotropic viruses in chimpanzees.
“A central role for CD8+ CTLs in virus elimination in the liver is further supported by experimental depletion studies, where depletion of CD8+ T cells delays the clearance of hepatotropic viruses in chimpanzees(131, 185).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [185]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Visualizing the generation of memory CD4 T cells in the whole body
Reinhardt, R. L., Khoruts, A., Merica, R., Zell, T., & Jenkins, M. K. (2001) · Nature · doi:10.1038/35065111 · Cited by 1,026 · cited 1×
“Studies in mice revealed that memory T cells can reside in tissues for long periods of time where they could provide a rapid first line of defense upon reinfection (30, 31, 35, 36).”
Background
Flagged first, then by citations
Research works printed but not linked: 39
- 2001, N. Engl. J. Med., 345, 41, 10.1056/NEJM200107053450107 · DOI
- 2002, Proc. Natl. Acad. Sci. USA., 99, 15661, 10.1073/pnas.202608299 · DOI
- 1999, Immunity., 10, 439, 10.1016/S1074-7613(00)80044-8 · DOI
- 2001, J. Exp. Med., 194, 1395, 10.1084/jem.194.10.1395 · DOI
- 2000, J. Exp. Med., 191, 1499, 10.1084/jem.191.9.1499 · DOI
- 2000, J. Infect. Dis., 181, 1528, 10.1086/315450 · DOI
- 1995, Lancet., 346, 1006, 10.1016/S0140-6736(95)91691-1 · DOI
- 1999, Gastroenterology., 117, 933, 10.1016/S0016-5085(99)70353-7 · DOI
- 1999, J. Immunol., 162, 4177, 10.4049/jimmunol.162.7.4177 · DOI
- 2000, Eur. J. Immunol., 30, 2479, 10.1002/1521-4141(200009)30:9<2479::AID-IMMU2479>3.0.CO;2-B · DOI
- 2001, J. Virol., 75, 5550, 10.1128/JVI.75.12.5550-5558.2001 · DOI
- 2002, J. Immunol., 169, 3447, 10.4049/jimmunol.169.6.3447 · DOI
- 2002, J. Virol., 76, 12423, 10.1128/JVI.76.24.12423-12434.2002 · DOI
- 2001, Immunity., 15, 883, 10.1016/S1074-7613(01)00245-X · DOI
- 1995, Proc. Natl. Acad. Sci. USA., 92, 2755, 10.1073/pnas.92.7.2755 · DOI
- 1997, J. Clin. Invest., 100, 2376, 10.1172/JCI119778 · DOI
- 2002, Lancet., 359, 1478, 10.1016/S0140-6736(02)08435-0 · DOI
- 1992, J. Infect. Dis., 165, 438, 10.1093/infdis/165.3.438 · DOI
- 1992, Science., 258, 135, 10.1126/science.1279801 · DOI
- 2001, Hepatology., 33, 1479, 10.1053/jhep.2001.24371 · DOI
- 2001, J. Virol., 75, 7142, 10.1128/JVI.75.15.7142-7148.2001 · DOI
- 2002, J. Virol., 76, 6586, 10.1128/JVI.76.13.6586-6595.2002 · DOI
- 2003, J. Virol., 77, 862, 10.1128/JVI.77.2.862-870.2003 · DOI
- 1989, Science., 244, 359, 10.1126/science.2523562 · DOI
- 1999, Science., 283, 857, 10.1126/science.283.5403.857 · DOI
- 2003, J. Virol., 77, 68, 10.1128/JVI.77.1.68-76.2003 · DOI · Paper page
- 1992, Proc. Natl. Acad. Sci. USA., 89, 10011, 10.1073/pnas.89.21.10011 · DOI
- 1993, J. Gastroenterol. Hepatol., S33-S39
- 1993, J. Immunol., 151, 4189, 10.4049/jimmunol.151.8.4189 · DOI
- 2001, J. Exp. Med., 193, 981, 10.1084/jem.193.8.981 · DOI
- 2001, J. Immunol., 166, 1813, 10.4049/jimmunol.166.3.1813 · DOI
- 2002, Hepatology., 35, 694, 10.1053/jhep.2002.31770 · DOI
- 2003, J. Virol., 77, 1092, 10.1128/JVI.77.2.1092-1104.2003 · DOI
- 1998, J. Exp. Med., 188, 2199, 10.1084/jem.188.12.2199 · DOI · Paper page
- 2001, Science., 291, 2413, 10.1126/science.1058867 · DOI · Paper page
- 2002, Nat. Rev. Immunol., 2, 417, 10.1038/nri820 · DOI
- 2002, J. Exp. Med., 195, F49, 10.1084/jem.20020767 · DOI
- 2000, Nat. Med., 6, 578, 10.1038/75063 · DOI
- 2002, Nat. Rev. Immunol., 2, 283, 10.1038/nri779 · DOI
Cited by
Sorted by citations
Persistent cellular immunity to SARS-CoV-2 infection
Breton, G., Mendoza, P., Hägglöf, T., Oliveira, T. Y., Schaefer-Babajew, D., Gaebler, C., Turroja, M., Hurley, A., Caskey, M., & Nussenzweig, M. C. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202515 · Cited by 129
HCV-Specific T Cell Responses During and After Chronic HCV Infection
Luxenburger, H., Neumann-Haefelin, C., Thimme, R., & Boettler, T. (2018) · Viruses · doi:10.3390/v10110645 · Cited by 64
The liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59
Metadata
- Authors
- Shoukry, N. H., Grakoui, A., Houghton, M., Chien, D. Y., Ghrayeb, J., Reimann, K. A., & Walker, C. M.
- Affiliations
- Abigail Wexner Research Institute (US)
- Rockefeller University (US)
- 3Chiron Corporation, Emeryville, CA 94608
- 4Centocor, Malvern, PA 19355
- Beth Israel Deaconess Medical Center (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2003-06-16
- Volume
- 197
- Issue
- 12
- Pages
- 1645-1655
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2193956
- OpenAlex
- W2137929296
- Cited by
- 656
- References
- 1
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 19 · 2023: 14 · 2022: 12 · 2021: 18 · 2020: 25 · 2019: 28 · 2018: 25 · 2017: 26 · 2016: 32 · 2015: 26 · 2014: 33 · 2013: 42 · 2012: 34
- FWCI
- 24.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- American Liver Foundation
- Emory University
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Allergy and Infectious Diseases (U19AI048231, R01AI147367, U19 AI48231)
- National Center for Research Resources (R 24 RR16001, R24RR016001)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- hepatitis C virus, chronic hepatitis C, memory CD8+ T cells, cytotoxic T lymphocytes, CD4+ T helper cells, chimpanzees, virus-specific T cell responses, T cell depletion, viral clearance, protective immunity
- MeSH terms
- Animals, Epitopes, Pan troglodytes, Hepatitis C, Humans, Immunologic Memory, Time Factors, Virus Replication, CD4-Positive T-Lymphocytes, Hepacivirus, CD8-Positive T-Lymphocytes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
