Transcriptional Pattern Analysis of Virus-Specific CD8+ T Cells in Hepatitis C Infection: Increased Expression of TOX and Eomesodermin During and After Persistent Antigen Recognition Article Swipe
Nils H. Wildner
,
Andreas Walker
,
Franziska Brauneck
,
Vanessa Ditt
,
Sven Peine
,
Samuel Huber
,
Friedrich Haag
,
Claudia Beisel
,
Jörg Timm
,
Julian Schulze zur Wiesch
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.886646
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.886646
Thymocyte selection-associated high mobility group box (TOX) has been described to be a key regulator in the formation of CD8+ T cell exhaustion. Hepatitis C virus (HCV) infection with different lengths of antigen exposure in acute, chronic, and after resolution of HCV infection is the ideal immunological model to study the expression of TOX in HCV-specific CD8+ T cells with different exposure to antigen. HCV-specific CD8+ T cells from 35 HLA-A*01:01, HLA-A*02:01, and HLA-A*24:02 positive patients were analyzed with a 16-color FACS-panel evaluating the surface expression of lineage markers (CD3, CD8), ectoenzymes (CD39, CD73), markers of differentiation (CD45RO, CCR7, CD127), and markers of exhaustion and activation (TIGIT, PD-1, KLRG1, CD226) and transcription factors (TOX, Eomesodermin, T-bet). Here, we defined on-target T cells as T cells against epitopes without escape mutations and off-target T cells as those against a “historical” antigen mutated in the autologous sequence. TOX+HCV-specific CD8+ T cells from patients with chronic HCV and on-target T cells displayed co-expression of Eomesodermin and were associated with the formation of terminally exhausted CD127 - PD1 hi , CD39 hi , CD73 low CD8+ T cells. In contrast, TOX+HCV-specific CD8+ T cells in patients with off-target T cells represented a progenitor memory Tex phenotype characterized by CD127 hi expression and a CD39 low and CD73 hi phenotype. TOX+HCV-specified CD8+ T cells in patients with a sustained virologic response were characterized by a memory phenotype (CD127+, CD73 hi ) and co-expression of immune checkpoints and Eomesodermin, indicating a key structure in priming of HCV-specific CD8+ T cells in the chronic stage, which persisted as a residual after therapy. Overall, the occurrence of TOX+HCV-specific CD8+ T cells was revealed at each disease stage, which impacted the development of progenitor Tex, intermediate Tex, and terminally exhausted T cell through an individual molecular footprint. In sum, TOX is induced early during acute infection but is modulated by changes in viral sequence and antigen recognition. In the case of antigen persistence, the interaction with Eomesodermin leads to the formation of terminally exhausted virus-specific CD8+ T cells, and there was a direct correlation of the co-expression of TOX and Eomes and terminally exhausted phenotype of virus-specific CD8+ T cells.
Related Topics
Concepts
Interleukin-7 receptor
CD8
Immunology
TIGIT
Biology
Antigen
Cytotoxic T cell
T cell
Molecular biology
Virology
Immune system
IL-2 receptor
In vitro
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.886646
- https://www.frontiersin.org/articles/10.3389/fimmu.2022.886646/pdf
- OA Status
- gold
- Cited By
- 9
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4281661553
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4281661553Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2022.886646Digital Object Identifier
- Title
-
Transcriptional Pattern Analysis of Virus-Specific CD8+ T Cells in Hepatitis C Infection: Increased Expression of TOX and Eomesodermin During and After Persistent Antigen RecognitionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-06-06Full publication date if available
- Authors
-
Nils H. Wildner, Andreas Walker, Franziska Brauneck, Vanessa Ditt, Sven Peine, Samuel Huber, Friedrich Haag, Claudia Beisel, Jörg Timm, Julian Schulze zur WieschList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2022.886646Publisher landing page
- PDF URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2022.886646/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2022.886646/pdfDirect OA link when available
- Concepts
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Interleukin-7 receptor, CD8, Immunology, TIGIT, Biology, Antigen, Cytotoxic T cell, T cell, Molecular biology, Virology, Immune system, IL-2 receptor, In vitro, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2024: 3, 2023: 5, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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71Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2091172564, https://openalex.org/W2152441233, https://openalex.org/W2130259551, https://openalex.org/W1993617345, https://openalex.org/W2059384462, https://openalex.org/W2111359040, https://openalex.org/W2610783335, https://openalex.org/W1983695417, https://openalex.org/W2560785983, https://openalex.org/W3185265774, https://openalex.org/W3118328775, https://openalex.org/W2962915977, https://openalex.org/W2114098868, https://openalex.org/W4229663730, https://openalex.org/W2006774237, https://openalex.org/W3139828130, https://openalex.org/W2019446509, https://openalex.org/W2077116159, https://openalex.org/W1966644185, https://openalex.org/W3186514447, https://openalex.org/W2804786344, https://openalex.org/W2541574334, https://openalex.org/W2506616866, https://openalex.org/W2513922839, https://openalex.org/W2991888163, https://openalex.org/W6758346484, https://openalex.org/W2950413690, https://openalex.org/W2952815301, https://openalex.org/W2979874482, https://openalex.org/W2167827953, https://openalex.org/W1985680307, https://openalex.org/W2119896120, https://openalex.org/W3093964423, https://openalex.org/W3038223554, https://openalex.org/W1983096169, https://openalex.org/W2900635809, https://openalex.org/W2086556660, https://openalex.org/W2766745368, https://openalex.org/W2927728904, https://openalex.org/W3006887831, https://openalex.org/W2117200807, https://openalex.org/W3176745270, https://openalex.org/W3037289028, https://openalex.org/W2170856427, https://openalex.org/W2068560173, https://openalex.org/W2155285682, https://openalex.org/W1759807482, https://openalex.org/W2606239211, https://openalex.org/W3024428489, https://openalex.org/W1993835819, https://openalex.org/W3088020815, https://openalex.org/W1975753196, https://openalex.org/W2129220531, https://openalex.org/W3113043187, https://openalex.org/W2951598503, https://openalex.org/W2947617159, https://openalex.org/W2951520325, https://openalex.org/W2903754922, https://openalex.org/W2104966044, https://openalex.org/W2168343255, https://openalex.org/W2134122465, https://openalex.org/W3020888809, https://openalex.org/W2887408362, https://openalex.org/W2995490450, https://openalex.org/W3180586010, https://openalex.org/W3133312573, https://openalex.org/W2575481614, https://openalex.org/W2975736685, https://openalex.org/W2889555301, https://openalex.org/W2912648593, https://openalex.org/W992974879 |
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