Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation
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Exhausted CD8+ T cell responses during chronic viral infections are defined by a complex expression pattern of inhibitory receptors. However, very little information is currently available about the coexpression patterns of these receptors on human virus-specific CD8+ T cells and their correlation with antiviral functions, T cell differentiation and antigen recognition. We addressed these important aspects in a cohort of 38 chronically HCV infected patients and found a coexpression of inhibitory receptors such as 2B4, CD160 and KLRG1 in association with PD-1 in about half of the HCV-specific CD8+ T cell responses. Importantly, this exhaustive phenotype was associated with low and intermediate levels of CD127 expression, an impaired proliferative capacity, an intermediate T cell differentiation stage and absence of sequence variations within the corresponding epitopes, indicating ongoing antigen triggering. In contrast, a low expression of inhibitory receptors by the remaining HCV-specific CD8+ T cells occurred in concert with a CD127hi phenotype, an early T cell differentiation stage and presence of viral sequence variations within the corresponding epitopes. In sum, these results suggest that T cell exhaustion contributes to the failure of about half of HCV-specific CD8+ T cell responses and that it is determined by a complex interplay of immunological (e.g. T cell differentiation) and virological (e.g. ongoing antigen triggering) factors.
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Dysfunctional T cells express, to different degrees, inhibitory molecules including PD-1, Tim-3, LAG-3, 2B4, CD160, and KLRG-1.
“compelling evidence indicate that dysfunctional T cells express in different degrees the “inhibitory” molecules including PD-1, Tim-3, LAG-3, 2B4, CD160, and KLGR-1.”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [76]
Different categories of T cell abnormalities may be mechanistically intertwined.
“It suggests that different categories of T cell abnormalities may be mechanistically intertwined [28,74–76].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [76]
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- Authors
- Bengsch, B., Seigel, B., Ruhl, M., Timm, J., Kuntz, M., Blum, H. E., Pircher, H., & Thimme, R.
- Affiliations
- University of Freiburg (DE)
- University of Duisburg-Essen (DE)
- Corresponding author
- Thimme, Robert
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-10
- Volume
- 6
- Issue
- 6
- Pages
- e1000947
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2883597
- OpenAlex
- W1975753196
- Cited by
- 373
- References
- 40
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 24 · 2020: 26 · 2019: 23 · 2018: 26 · 2017: 19 · 2016: 18 · 2015: 40 · 2014: 47 · 2013: 32 · 2012: 31
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (GSC‐4, TH-719/3-1, GSC-4/Spemann Graduate School)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- T cell exhaustion, inhibitory receptors, PD-1, 2B4, CD160, KLRG1, CD127, T cell differentiation, antigen recognition, chronic hepatitis C
- MeSH terms
- Signaling Lymphocytic Activation Molecule Family, Cell Differentiation, Flow Cytometry, Hepatitis C, Humans, Lymphocyte Activation, Receptors, Immunologic, T-Lymphocytes, Trans-Activators, Antigens, CD, Hepacivirus, CD8-Positive T-Lymphocytes, Viral Load, Lectins, C-Type, Cell Proliferation, Apoptosis Regulatory Proteins, GPI-Linked Proteins, Programmed Cell Death 1 Receptor
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