Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis
Hepatitis C virus (HCV)‐specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are the main effectors of liver fibrosis. TGFβ, produced by HCV‐specific CD8+ T cells, is a key regulatory cytokine modulating HCV‐specific effector T cells. Here we s...
Gespeichert in:
Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2012-12, Vol.56 (6), p.2094-2105 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2105 |
---|---|
container_issue | 6 |
container_start_page | 2094 |
container_title | Hepatology (Baltimore, Md.) |
container_volume | 56 |
creator | Li, Shaoyong Vriend, Lianne E.M. Nasser, Imad A. Popov, Yury Afdhal, Nezam H. Koziel, Margaret J. Schuppan, Detlef Exley, Mark A. Alatrakchi, Nadia |
description | Hepatitis C virus (HCV)‐specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are the main effectors of liver fibrosis. TGFβ, produced by HCV‐specific CD8+ T cells, is a key regulatory cytokine modulating HCV‐specific effector T cells. Here we studied TGFβ as well as other factors produced by HCV‐specific intrahepatic lymphocytes (IHL) and peripheral blood cells in hepatic inflammation and fibrogenesis. This was a cross‐sectional study of two well‐defined groups of HCV‐infected subjects with slow (≤0.1 Metavir units/year, n = 13) or rapid (n = 6) liver fibrosis progression. HCV‐specific T‐cell responses were studied using interferon‐gamma (IFNγ)‐ELISpot ±monoclonal antibodies (mAbs) blocking regulatory cytokines, along with multiplex, enzyme‐linked immunosorbent assay (ELISA) and multiparameter fluorescence‐activated cell sorting (FACS). The effects of IHL stimulated with HCV‐core peptides on HSC expression of profibrotic and fibrolytic genes were determined. Blocking regulatory cytokines significantly raised detection of HCV‐specific effector (IFNγ) responses only in slow fibrosis progressors, both in the periphery (P = 0.003) and liver (P = 0.01). Regulatory cytokine blockade revealed HCV‐specific IFNγ responses strongly correlated with HCV‐specific TGFβ, measured before blockade (R = 0.84, P = 0.0003), with only a trend to correlation with HCV‐specific IL‐10. HCV‐specific TGFβ was produced by CD8 and CD4 T cells. HCV‐specific TGFβ, not interleukin (IL)‐10, inversely correlated with liver inflammation (R = −0.63, P = 0.008) and, unexpectedly, fibrosis (R = −0.46, P = 0.05). In addition, supernatants from HCV‐stimulated IHL of slow progressors specifically increased fibrolytic gene expression in HSC and treatment with anti‐TGFβ mAb abrogated such expression. Conclusion: Although TGFβ is considered a major profibrogenic cytokine, local production of TGFβ by HCV‐specific T cells appeared to have a protective role in HCV‐infected liver, together with other T‐cell‐derived factors, ameliorating HCV liver disease progression. (HEPATOLOGY 2012;56:2094–2105) |
doi_str_mv | 10.1002/hep.25951 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3508175</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2831418491</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4771-6e720ca9a46de1f46487413da073b0fdd087482a0bc4fc47e6051f5e9ead6c983</originalsourceid><addsrcrecordid>eNpdkkuP0zAUhS0EYsrAgj-ALCEkNpnxI3aSDRIaDS1SNSAeYmk5znXrIY2DnbQz_36ctpTHyrbud47vPTZCLym5oISwyzX0F0xUgj5CMypYkXEuyGM0I6wgWUV5dYaexXhLCKlyVj5FZ4yVRJaczNB2Ab0e3OAiNnjrwhiz2INx1hk8ZAbaNmsguC00eAi6i9aHjetWeBX8blhjq83gA65h0DhZ6Bi9cXpI9M6lcmz9Dq_3NxhsXR38CjqILj5HT6xuI7w4rufo-4frb1eLbPlp_vHq_TIzeVHQTELBiNGVzmUD1OYyL4uc8kaTgtfENg1J55JpUpvcJglIIqgVUIFupKlKfo7eHXz7sd5AY6BLU7SqD26jw73y2ql_K51bq5XfqhRgSQuRDN4eDYL_NUIc1MbFKRbdgR-joozxnDORy4S-_g-99WPo0ngTRYUUgkyGr_7u6NTK7ydJwJsjoKPRrU2pGxf_cLIUnLCJuzxwO9fC_alOiZr-hEqpq_2fUIvrz_tNUmQHhYsD3J0UOvxUsuCFUD9u5upLJb_OlzdcVfwBv6u6AA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1221565505</pqid></control><display><type>article</type><title>Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Li, Shaoyong ; Vriend, Lianne E.M. ; Nasser, Imad A. ; Popov, Yury ; Afdhal, Nezam H. ; Koziel, Margaret J. ; Schuppan, Detlef ; Exley, Mark A. ; Alatrakchi, Nadia</creator><creatorcontrib>Li, Shaoyong ; Vriend, Lianne E.M. ; Nasser, Imad A. ; Popov, Yury ; Afdhal, Nezam H. ; Koziel, Margaret J. ; Schuppan, Detlef ; Exley, Mark A. ; Alatrakchi, Nadia</creatorcontrib><description>Hepatitis C virus (HCV)‐specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are the main effectors of liver fibrosis. TGFβ, produced by HCV‐specific CD8+ T cells, is a key regulatory cytokine modulating HCV‐specific effector T cells. Here we studied TGFβ as well as other factors produced by HCV‐specific intrahepatic lymphocytes (IHL) and peripheral blood cells in hepatic inflammation and fibrogenesis. This was a cross‐sectional study of two well‐defined groups of HCV‐infected subjects with slow (≤0.1 Metavir units/year, n = 13) or rapid (n = 6) liver fibrosis progression. HCV‐specific T‐cell responses were studied using interferon‐gamma (IFNγ)‐ELISpot ±monoclonal antibodies (mAbs) blocking regulatory cytokines, along with multiplex, enzyme‐linked immunosorbent assay (ELISA) and multiparameter fluorescence‐activated cell sorting (FACS). The effects of IHL stimulated with HCV‐core peptides on HSC expression of profibrotic and fibrolytic genes were determined. Blocking regulatory cytokines significantly raised detection of HCV‐specific effector (IFNγ) responses only in slow fibrosis progressors, both in the periphery (P = 0.003) and liver (P = 0.01). Regulatory cytokine blockade revealed HCV‐specific IFNγ responses strongly correlated with HCV‐specific TGFβ, measured before blockade (R = 0.84, P = 0.0003), with only a trend to correlation with HCV‐specific IL‐10. HCV‐specific TGFβ was produced by CD8 and CD4 T cells. HCV‐specific TGFβ, not interleukin (IL)‐10, inversely correlated with liver inflammation (R = −0.63, P = 0.008) and, unexpectedly, fibrosis (R = −0.46, P = 0.05). In addition, supernatants from HCV‐stimulated IHL of slow progressors specifically increased fibrolytic gene expression in HSC and treatment with anti‐TGFβ mAb abrogated such expression. Conclusion: Although TGFβ is considered a major profibrogenic cytokine, local production of TGFβ by HCV‐specific T cells appeared to have a protective role in HCV‐infected liver, together with other T‐cell‐derived factors, ameliorating HCV liver disease progression. (HEPATOLOGY 2012;56:2094–2105)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.25951</identifier><identifier>PMID: 22806830</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Biological and medical sciences ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Collagen Type I - genetics ; Cross-Sectional Studies ; Cytokines ; Disease Progression ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression ; Hepacivirus - immunology ; Hepatic Stellate Cells - metabolism ; Hepatitis ; Hepatitis C ; Hepatitis C, Chronic - immunology ; Hepatitis C, Chronic - metabolism ; Hepatitis C, Chronic - pathology ; Hepatology ; Humans ; Interferon-gamma - metabolism ; Interleukin-10 - metabolism ; Liver - immunology ; Liver - metabolism ; Liver cirrhosis ; Liver Cirrhosis - immunology ; Liver Cirrhosis - metabolism ; Liver Cirrhosis - pathology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Lymphocytes ; Male ; Matrix Metalloproteinase 1 - genetics ; Medical sciences ; Middle Aged ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Transforming Growth Factor beta - metabolism ; Viral Core Proteins - immunology</subject><ispartof>Hepatology (Baltimore, Md.), 2012-12, Vol.56 (6), p.2094-2105</ispartof><rights>Copyright © 2012 American Association for the Study of Liver Diseases</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4771-6e720ca9a46de1f46487413da073b0fdd087482a0bc4fc47e6051f5e9ead6c983</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.25951$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.25951$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26853020$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22806830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Shaoyong</creatorcontrib><creatorcontrib>Vriend, Lianne E.M.</creatorcontrib><creatorcontrib>Nasser, Imad A.</creatorcontrib><creatorcontrib>Popov, Yury</creatorcontrib><creatorcontrib>Afdhal, Nezam H.</creatorcontrib><creatorcontrib>Koziel, Margaret J.</creatorcontrib><creatorcontrib>Schuppan, Detlef</creatorcontrib><creatorcontrib>Exley, Mark A.</creatorcontrib><creatorcontrib>Alatrakchi, Nadia</creatorcontrib><title>Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Hepatitis C virus (HCV)‐specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are the main effectors of liver fibrosis. TGFβ, produced by HCV‐specific CD8+ T cells, is a key regulatory cytokine modulating HCV‐specific effector T cells. Here we studied TGFβ as well as other factors produced by HCV‐specific intrahepatic lymphocytes (IHL) and peripheral blood cells in hepatic inflammation and fibrogenesis. This was a cross‐sectional study of two well‐defined groups of HCV‐infected subjects with slow (≤0.1 Metavir units/year, n = 13) or rapid (n = 6) liver fibrosis progression. HCV‐specific T‐cell responses were studied using interferon‐gamma (IFNγ)‐ELISpot ±monoclonal antibodies (mAbs) blocking regulatory cytokines, along with multiplex, enzyme‐linked immunosorbent assay (ELISA) and multiparameter fluorescence‐activated cell sorting (FACS). The effects of IHL stimulated with HCV‐core peptides on HSC expression of profibrotic and fibrolytic genes were determined. Blocking regulatory cytokines significantly raised detection of HCV‐specific effector (IFNγ) responses only in slow fibrosis progressors, both in the periphery (P = 0.003) and liver (P = 0.01). Regulatory cytokine blockade revealed HCV‐specific IFNγ responses strongly correlated with HCV‐specific TGFβ, measured before blockade (R = 0.84, P = 0.0003), with only a trend to correlation with HCV‐specific IL‐10. HCV‐specific TGFβ was produced by CD8 and CD4 T cells. HCV‐specific TGFβ, not interleukin (IL)‐10, inversely correlated with liver inflammation (R = −0.63, P = 0.008) and, unexpectedly, fibrosis (R = −0.46, P = 0.05). In addition, supernatants from HCV‐stimulated IHL of slow progressors specifically increased fibrolytic gene expression in HSC and treatment with anti‐TGFβ mAb abrogated such expression. Conclusion: Although TGFβ is considered a major profibrogenic cytokine, local production of TGFβ by HCV‐specific T cells appeared to have a protective role in HCV‐infected liver, together with other T‐cell‐derived factors, ameliorating HCV liver disease progression. (HEPATOLOGY 2012;56:2094–2105)</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Collagen Type I - genetics</subject><subject>Cross-Sectional Studies</subject><subject>Cytokines</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression</subject><subject>Hepacivirus - immunology</subject><subject>Hepatic Stellate Cells - metabolism</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C, Chronic - immunology</subject><subject>Hepatitis C, Chronic - metabolism</subject><subject>Hepatitis C, Chronic - pathology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin-10 - metabolism</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - immunology</subject><subject>Liver Cirrhosis - metabolism</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Matrix Metalloproteinase 1 - genetics</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Viral Core Proteins - immunology</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkkuP0zAUhS0EYsrAgj-ALCEkNpnxI3aSDRIaDS1SNSAeYmk5znXrIY2DnbQz_36ctpTHyrbud47vPTZCLym5oISwyzX0F0xUgj5CMypYkXEuyGM0I6wgWUV5dYaexXhLCKlyVj5FZ4yVRJaczNB2Ab0e3OAiNnjrwhiz2INx1hk8ZAbaNmsguC00eAi6i9aHjetWeBX8blhjq83gA65h0DhZ6Bi9cXpI9M6lcmz9Dq_3NxhsXR38CjqILj5HT6xuI7w4rufo-4frb1eLbPlp_vHq_TIzeVHQTELBiNGVzmUD1OYyL4uc8kaTgtfENg1J55JpUpvcJglIIqgVUIFupKlKfo7eHXz7sd5AY6BLU7SqD26jw73y2ql_K51bq5XfqhRgSQuRDN4eDYL_NUIc1MbFKRbdgR-joozxnDORy4S-_g-99WPo0ngTRYUUgkyGr_7u6NTK7ydJwJsjoKPRrU2pGxf_cLIUnLCJuzxwO9fC_alOiZr-hEqpq_2fUIvrz_tNUmQHhYsD3J0UOvxUsuCFUD9u5upLJb_OlzdcVfwBv6u6AA</recordid><startdate>201212</startdate><enddate>201212</enddate><creator>Li, Shaoyong</creator><creator>Vriend, Lianne E.M.</creator><creator>Nasser, Imad A.</creator><creator>Popov, Yury</creator><creator>Afdhal, Nezam H.</creator><creator>Koziel, Margaret J.</creator><creator>Schuppan, Detlef</creator><creator>Exley, Mark A.</creator><creator>Alatrakchi, Nadia</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wolters Kluwer Health, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201212</creationdate><title>Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis</title><author>Li, Shaoyong ; Vriend, Lianne E.M. ; Nasser, Imad A. ; Popov, Yury ; Afdhal, Nezam H. ; Koziel, Margaret J. ; Schuppan, Detlef ; Exley, Mark A. ; Alatrakchi, Nadia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4771-6e720ca9a46de1f46487413da073b0fdd087482a0bc4fc47e6051f5e9ead6c983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Collagen Type I - genetics</topic><topic>Cross-Sectional Studies</topic><topic>Cytokines</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression</topic><topic>Hepacivirus - immunology</topic><topic>Hepatic Stellate Cells - metabolism</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C, Chronic - immunology</topic><topic>Hepatitis C, Chronic - metabolism</topic><topic>Hepatitis C, Chronic - pathology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin-10 - metabolism</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - immunology</topic><topic>Liver Cirrhosis - metabolism</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Matrix Metalloproteinase 1 - genetics</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Viral Core Proteins - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Shaoyong</creatorcontrib><creatorcontrib>Vriend, Lianne E.M.</creatorcontrib><creatorcontrib>Nasser, Imad A.</creatorcontrib><creatorcontrib>Popov, Yury</creatorcontrib><creatorcontrib>Afdhal, Nezam H.</creatorcontrib><creatorcontrib>Koziel, Margaret J.</creatorcontrib><creatorcontrib>Schuppan, Detlef</creatorcontrib><creatorcontrib>Exley, Mark A.</creatorcontrib><creatorcontrib>Alatrakchi, Nadia</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Shaoyong</au><au>Vriend, Lianne E.M.</au><au>Nasser, Imad A.</au><au>Popov, Yury</au><au>Afdhal, Nezam H.</au><au>Koziel, Margaret J.</au><au>Schuppan, Detlef</au><au>Exley, Mark A.</au><au>Alatrakchi, Nadia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2012-12</date><risdate>2012</risdate><volume>56</volume><issue>6</issue><spage>2094</spage><epage>2105</epage><pages>2094-2105</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Hepatitis C virus (HCV)‐specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are the main effectors of liver fibrosis. TGFβ, produced by HCV‐specific CD8+ T cells, is a key regulatory cytokine modulating HCV‐specific effector T cells. Here we studied TGFβ as well as other factors produced by HCV‐specific intrahepatic lymphocytes (IHL) and peripheral blood cells in hepatic inflammation and fibrogenesis. This was a cross‐sectional study of two well‐defined groups of HCV‐infected subjects with slow (≤0.1 Metavir units/year, n = 13) or rapid (n = 6) liver fibrosis progression. HCV‐specific T‐cell responses were studied using interferon‐gamma (IFNγ)‐ELISpot ±monoclonal antibodies (mAbs) blocking regulatory cytokines, along with multiplex, enzyme‐linked immunosorbent assay (ELISA) and multiparameter fluorescence‐activated cell sorting (FACS). The effects of IHL stimulated with HCV‐core peptides on HSC expression of profibrotic and fibrolytic genes were determined. Blocking regulatory cytokines significantly raised detection of HCV‐specific effector (IFNγ) responses only in slow fibrosis progressors, both in the periphery (P = 0.003) and liver (P = 0.01). Regulatory cytokine blockade revealed HCV‐specific IFNγ responses strongly correlated with HCV‐specific TGFβ, measured before blockade (R = 0.84, P = 0.0003), with only a trend to correlation with HCV‐specific IL‐10. HCV‐specific TGFβ was produced by CD8 and CD4 T cells. HCV‐specific TGFβ, not interleukin (IL)‐10, inversely correlated with liver inflammation (R = −0.63, P = 0.008) and, unexpectedly, fibrosis (R = −0.46, P = 0.05). In addition, supernatants from HCV‐stimulated IHL of slow progressors specifically increased fibrolytic gene expression in HSC and treatment with anti‐TGFβ mAb abrogated such expression. Conclusion: Although TGFβ is considered a major profibrogenic cytokine, local production of TGFβ by HCV‐specific T cells appeared to have a protective role in HCV‐infected liver, together with other T‐cell‐derived factors, ameliorating HCV liver disease progression. (HEPATOLOGY 2012;56:2094–2105)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22806830</pmid><doi>10.1002/hep.25951</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0270-9139 |
ispartof | Hepatology (Baltimore, Md.), 2012-12, Vol.56 (6), p.2094-2105 |
issn | 0270-9139 1527-3350 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3508175 |
source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals |
subjects | Adult Aged Biological and medical sciences CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Collagen Type I - genetics Cross-Sectional Studies Cytokines Disease Progression Female Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Hepacivirus - immunology Hepatic Stellate Cells - metabolism Hepatitis Hepatitis C Hepatitis C, Chronic - immunology Hepatitis C, Chronic - metabolism Hepatitis C, Chronic - pathology Hepatology Humans Interferon-gamma - metabolism Interleukin-10 - metabolism Liver - immunology Liver - metabolism Liver cirrhosis Liver Cirrhosis - immunology Liver Cirrhosis - metabolism Liver Cirrhosis - pathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Lymphocytes Male Matrix Metalloproteinase 1 - genetics Medical sciences Middle Aged T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Transforming Growth Factor beta - metabolism Viral Core Proteins - immunology |
title | Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T10%3A02%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hepatitis%20c%20virus-specific%20t-cell-derived%20transforming%20growth%20factor%20beta%20is%20associated%20with%20slow%20hepatic%20fibrogenesis&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=Li,%20Shaoyong&rft.date=2012-12&rft.volume=56&rft.issue=6&rft.spage=2094&rft.epage=2105&rft.pages=2094-2105&rft.issn=0270-9139&rft.eissn=1527-3350&rft.coden=HPTLD9&rft_id=info:doi/10.1002/hep.25951&rft_dat=%3Cproquest_pubme%3E2831418491%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1221565505&rft_id=info:pmid/22806830&rfr_iscdi=true |