Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B
Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CH...
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| Veröffentlicht in: | Journal of medical virology 2024-03, Vol.96 (3), p.e29515-n/a |
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| creator | Wang, Li‐Tzu Chen, Yu‐Hong Cheng, Yang Fan, Hsiu‐Lung Chen, Teng‐Wei Shih, Yu‐Lueng Hsieh, Tsai‐Yuan Huang, Wen‐Yen Huang, Wei‐Chen |
| description | Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management. |
| doi_str_mv | 10.1002/jmv.29515 |
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The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.29515</identifier><identifier>PMID: 38469923</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Antigens ; Bioinformatics ; CD38 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cell signaling ; Chronic infection ; Core protein ; Correlation analysis ; Epitopes ; Genotypes ; HBcAg ; HBV ; Hepatitis ; Hepatitis B ; Hepatitis B Core Antigens ; Hepatitis B virus - genetics ; Hepatitis B, Chronic ; Hepatocytes ; Humans ; Immune response ; Immune system ; Inflammation ; Longitudinal Studies ; Lymphocytes ; Lymphocytes T ; PD‐1 ; Peptides ; Programmed Cell Death 1 Receptor - genetics ; Proteins ; T cells</subject><ispartof>Journal of medical virology, 2024-03, Vol.96 (3), p.e29515-n/a</ispartof><rights>2024 The Authors. published by Wiley Periodicals LLC.</rights><rights>2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3485-d9769e3665676e147c35d7992aaa0cd6bf3a4bb4ecfc61bc6ed5e92b633bf33f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.29515$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.29515$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38469923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Li‐Tzu</creatorcontrib><creatorcontrib>Chen, Yu‐Hong</creatorcontrib><creatorcontrib>Cheng, Yang</creatorcontrib><creatorcontrib>Fan, Hsiu‐Lung</creatorcontrib><creatorcontrib>Chen, Teng‐Wei</creatorcontrib><creatorcontrib>Shih, Yu‐Lueng</creatorcontrib><creatorcontrib>Hsieh, Tsai‐Yuan</creatorcontrib><creatorcontrib>Huang, Wen‐Yen</creatorcontrib><creatorcontrib>Huang, Wei‐Chen</creatorcontrib><title>Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.</description><subject>Antigens</subject><subject>Bioinformatics</subject><subject>CD38 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cell signaling</subject><subject>Chronic infection</subject><subject>Core protein</subject><subject>Correlation analysis</subject><subject>Epitopes</subject><subject>Genotypes</subject><subject>HBcAg</subject><subject>HBV</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B Core Antigens</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B, Chronic</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Longitudinal Studies</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>PD‐1</subject><subject>Peptides</subject><subject>Programmed Cell Death 1 Receptor - genetics</subject><subject>Proteins</subject><subject>T cells</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1OxCAYRYnR6Piz8AUMiRtdVKG0tCx14m80btQtofSrw6QtFdoxxo2P4DP6JDKOGmPiCgiHw813Edqm5IASEh9Om9lBLFKaLqERJYJHgmR0GY0ITXjEOU3X0Lr3U0JILuJ4Fa2xPOFCxGyEXsa1aY1WNTZNV4dNb2zrsa3wBLpw6I3Hx3hm3OCxtg6wanvzAO3761sDpVE9lOFlM7Q20BNb2wej8S3WUNfYge-CDDw2LdYTZ8NHv7WbaKVStYetr3UD3Z2e3I7Po6ubs4vx0VWkWZKnUSkyLoBxnvKMA00yzdIyC_GVUkSXvKiYSooiAV1pTgvNoUxBxAVnLFyxim2gvYW3c_ZxAN_Lxvh5QtWCHbwMowszynLGA7r7B53awbUhnWSEMMbyLJlT-wtKO-u9g0p2zjTKPUtK5LwRGRqRn40EdufLOBRhYj_kdwUBOFwAT6aG5_9N8vL6fqH8AKitmDI</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Wang, Li‐Tzu</creator><creator>Chen, Yu‐Hong</creator><creator>Cheng, Yang</creator><creator>Fan, Hsiu‐Lung</creator><creator>Chen, Teng‐Wei</creator><creator>Shih, Yu‐Lueng</creator><creator>Hsieh, Tsai‐Yuan</creator><creator>Huang, Wen‐Yen</creator><creator>Huang, Wei‐Chen</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>202403</creationdate><title>Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B</title><author>Wang, Li‐Tzu ; Chen, Yu‐Hong ; Cheng, Yang ; Fan, Hsiu‐Lung ; Chen, Teng‐Wei ; Shih, Yu‐Lueng ; Hsieh, Tsai‐Yuan ; Huang, Wen‐Yen ; Huang, Wei‐Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3485-d9769e3665676e147c35d7992aaa0cd6bf3a4bb4ecfc61bc6ed5e92b633bf33f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antigens</topic><topic>Bioinformatics</topic><topic>CD38 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>Cell signaling</topic><topic>Chronic infection</topic><topic>Core protein</topic><topic>Correlation analysis</topic><topic>Epitopes</topic><topic>Genotypes</topic><topic>HBcAg</topic><topic>HBV</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B Core Antigens</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B, Chronic</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Inflammation</topic><topic>Longitudinal Studies</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>PD‐1</topic><topic>Peptides</topic><topic>Programmed Cell Death 1 Receptor - genetics</topic><topic>Proteins</topic><topic>T cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Li‐Tzu</creatorcontrib><creatorcontrib>Chen, Yu‐Hong</creatorcontrib><creatorcontrib>Cheng, Yang</creatorcontrib><creatorcontrib>Fan, Hsiu‐Lung</creatorcontrib><creatorcontrib>Chen, Teng‐Wei</creatorcontrib><creatorcontrib>Shih, Yu‐Lueng</creatorcontrib><creatorcontrib>Hsieh, Tsai‐Yuan</creatorcontrib><creatorcontrib>Huang, Wen‐Yen</creatorcontrib><creatorcontrib>Huang, Wei‐Chen</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Li‐Tzu</au><au>Chen, Yu‐Hong</au><au>Cheng, Yang</au><au>Fan, Hsiu‐Lung</au><au>Chen, Teng‐Wei</au><au>Shih, Yu‐Lueng</au><au>Hsieh, Tsai‐Yuan</au><au>Huang, Wen‐Yen</au><au>Huang, Wei‐Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2024-03</date><risdate>2024</risdate><volume>96</volume><issue>3</issue><spage>e29515</spage><epage>n/a</epage><pages>e29515-n/a</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38469923</pmid><doi>10.1002/jmv.29515</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antigens Bioinformatics CD38 antigen CD8 antigen CD8-Positive T-Lymphocytes Cell signaling Chronic infection Core protein Correlation analysis Epitopes Genotypes HBcAg HBV Hepatitis Hepatitis B Hepatitis B Core Antigens Hepatitis B virus - genetics Hepatitis B, Chronic Hepatocytes Humans Immune response Immune system Inflammation Longitudinal Studies Lymphocytes Lymphocytes T PD‐1 Peptides Programmed Cell Death 1 Receptor - genetics Proteins T cells |
| title | Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B |
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