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Cited by 217Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyHepatitis B Virus Studies

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+ T cells and successful immunotherapy against chronic viral liver infection

Huang, Li-Rung, Wohlleber, Dirk, Reisinger, Florian, Jenne, Craig N, Cheng, Ru-Lin, Abdullah, Zeinab, Schildberg, Frank A, Odenthal, Margarete, Dienes, Hans-Peter, van Rooijen, Nico, Schmitt, Edgar, Garbi, Natalio, Croft, Michael, Kurts, Christian, Kubes, Paul, Protzer, Ulrike, Heikenwalder, Mathias, Knolle, Percy A·2013·Nature Immunology
DOI 10.1038/ni.2573
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Abstract

Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intrahepatic myeloid-cell aggregates for T cell population expansion') without causing immunopathology. In the liver, CTL proliferation was restricted to iMATEs that were composed of inflammatory monocyte-derived CD11b(+) cells. Signaling via tumor-necrosis factor (TNF) caused iMATE formation that facilitated costimulation dependent on the receptor OX40 for expansion of the CTL population. The iMATEs arose during acute viral infection but were absent during chronic viral infection, yet they were still induced by TLR signaling. Such hepatic expansion of the CTL population controlled chronic viral infection of the liver after vaccination with DNA. Thus, iMATEs are dynamic structures that overcome regulatory cues that limit the population expansion of CTLs during chronic infection and can be used in new therapeutic vaccination strategies.

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Metadata

Authors
Huang, L.-R., Wohlleber, D., Reisinger, F., Jenne, C. N., Cheng, R.-L., Abdullah, Z., Schildberg, F. A., Odenthal, M., Dienes, H.-P., van Rooijen, N., Schmitt, E., Garbi, N., Croft, M., Kurts, C., Kubes, P., Protzer, U., Heikenwalder, M., & Knolle, P. A.
Affiliations
  • University of Bonn (DE)
  • Helmholtz Munich (DE)
  • University of Calgary (CA)
  • University of Cologne (DE)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Johannes Gutenberg University Mainz (DE)
  • La Jolla Institute for Immunology (US)
Corresponding author
Knolle, Percy A
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2013-04-14
Volume
14
Issue
6
Pages
574-583
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2573
OpenAlex
W2049247030
Cited by
216
References
38
Citations by year
2026: 5 · 2025: 6 · 2024: 13 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 13 · 2019: 16 · 2018: 30 · 2017: 23 · 2016: 24 · 2015: 19 · 2014: 15 · 2013: 9
FWCI
12.36
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • Site cant be reached (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
CD8+ T cell proliferation, Toll-like receptor signaling, TNF-α, cytotoxic T lymphocytes, DNA vaccine, immunotherapy, liver
MeSH terms
Animals, Animals, Newborn, Chronic Disease, Flow Cytometry, Immunotherapy, Liver, Liver Diseases, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Cytotoxic, Signal Transduction, Mice, Knockout, CD8-Positive T-Lymphocytes, Microscopy, Confocal, Myeloid Cells, CD11b Antigen, Cell Proliferation, Green Fluorescent Proteins, Toll-Like Receptor 9, Mice, Receptors, OX40, Host-Pathogen Interactions

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