Immunosurveillance of the liver by intravascular effector CD8(+) T cells
Effector CD8(+) T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show...
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| Veröffentlicht in: | Cell 2015-04, Vol.161 (3), p.486-500 |
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| creator | Guidotti, Luca G Inverso, Donato Sironi, Laura Di Lucia, Pietro Fioravanti, Jessica Ganzer, Lucia Fiocchi, Amleto Vacca, Maurizio Aiolfi, Roberto Sammicheli, Stefano Mainetti, Marta Cataudella, Tiziana Raimondi, Andrea Gonzalez-Aseguinolaza, Gloria Protzer, Ulrike Ruggeri, Zaverio M Chisari, Francis V Isogawa, Masanori Sitia, Giovanni Iannacone, Matteo |
| description | Effector CD8(+) T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes. |
| doi_str_mv | 10.1016/j.cell.2015.03.005 |
| format | Article |
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Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.</description><identifier>ISSN: 0092-8674</identifier><identifier>ISSN: 1097-4172</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2015.03.005</identifier><identifier>PMID: 25892224</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; CD8-Positive T-Lymphocytes - immunology ; Cell Movement ; Endothelial Cells - metabolism ; Hepatitis B - immunology ; Hepatitis B - pathology ; Hepatitis B virus - physiology ; Hepatocytes - metabolism ; Hyaluronic Acid - metabolism ; Liver - cytology ; Liver - immunology ; Liver Cirrhosis ; Mice ; Mice, Inbred C57BL ; Monitoring, Immunologic ; Platelet Adhesiveness ; Specific Pathogen-Free Organisms</subject><ispartof>Cell, 2015-04, Vol.161 (3), p.486-500</ispartof><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-b01af78264f1c997aea982f772d29a19415dac9e11aa328b6abc5479b360b66e3</citedby><cites>FETCH-LOGICAL-c473t-b01af78264f1c997aea982f772d29a19415dac9e11aa328b6abc5479b360b66e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25892224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guidotti, Luca G</creatorcontrib><creatorcontrib>Inverso, Donato</creatorcontrib><creatorcontrib>Sironi, Laura</creatorcontrib><creatorcontrib>Di Lucia, Pietro</creatorcontrib><creatorcontrib>Fioravanti, Jessica</creatorcontrib><creatorcontrib>Ganzer, Lucia</creatorcontrib><creatorcontrib>Fiocchi, Amleto</creatorcontrib><creatorcontrib>Vacca, Maurizio</creatorcontrib><creatorcontrib>Aiolfi, Roberto</creatorcontrib><creatorcontrib>Sammicheli, Stefano</creatorcontrib><creatorcontrib>Mainetti, Marta</creatorcontrib><creatorcontrib>Cataudella, Tiziana</creatorcontrib><creatorcontrib>Raimondi, Andrea</creatorcontrib><creatorcontrib>Gonzalez-Aseguinolaza, Gloria</creatorcontrib><creatorcontrib>Protzer, Ulrike</creatorcontrib><creatorcontrib>Ruggeri, Zaverio M</creatorcontrib><creatorcontrib>Chisari, Francis V</creatorcontrib><creatorcontrib>Isogawa, Masanori</creatorcontrib><creatorcontrib>Sitia, Giovanni</creatorcontrib><creatorcontrib>Iannacone, Matteo</creatorcontrib><title>Immunosurveillance of the liver by intravascular effector CD8(+) T cells</title><title>Cell</title><addtitle>Cell</addtitle><description>Effector CD8(+) T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.</description><subject>Animals</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Movement</subject><subject>Endothelial Cells - metabolism</subject><subject>Hepatitis B - immunology</subject><subject>Hepatitis B - pathology</subject><subject>Hepatitis B virus - physiology</subject><subject>Hepatocytes - metabolism</subject><subject>Hyaluronic Acid - metabolism</subject><subject>Liver - cytology</subject><subject>Liver - immunology</subject><subject>Liver Cirrhosis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monitoring, Immunologic</subject><subject>Platelet Adhesiveness</subject><subject>Specific Pathogen-Free Organisms</subject><issn>0092-8674</issn><issn>1097-4172</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIlscPcEA-FqGEXTux4xNC5dFKSFzK2XJcB1LlUeykUv-eRoUKTnvYmdmZHUKuEGIEFHer2LqqihlgGgOPAdIjMkZQMkpQsmMyBlAsyoRMRuQshBUAZGmanpIRSzPFGEvGZDav675pQ-83rqwq01hH24J2n45W5cZ5mm9p2XTebEywfWU8dUXhbNd6On3MJrc3dEEHF-GCnBSmCu7yZ56T9-enxXQWvb69zKcPr5FNJO-iHNAUMmMiKdAqJY0zKmOFlGzJlEGVYLo0VjlEYzjLcmFymyZS5VxALoTj5-R-r7vu89otrRvMVXrty9r4rW5Nqf9vmvJTf7QbjSg4ZMh2CpMfBd9-9S50ui7DkME0ru2DRiEF50pisoOyPdT6NgTvisMdBD10oFd6YOqhAw1c7zrYka7_OjxQfp_OvwH-EoPm</recordid><startdate>20150423</startdate><enddate>20150423</enddate><creator>Guidotti, Luca G</creator><creator>Inverso, Donato</creator><creator>Sironi, Laura</creator><creator>Di Lucia, Pietro</creator><creator>Fioravanti, Jessica</creator><creator>Ganzer, Lucia</creator><creator>Fiocchi, Amleto</creator><creator>Vacca, Maurizio</creator><creator>Aiolfi, Roberto</creator><creator>Sammicheli, Stefano</creator><creator>Mainetti, Marta</creator><creator>Cataudella, Tiziana</creator><creator>Raimondi, Andrea</creator><creator>Gonzalez-Aseguinolaza, Gloria</creator><creator>Protzer, Ulrike</creator><creator>Ruggeri, Zaverio M</creator><creator>Chisari, Francis V</creator><creator>Isogawa, Masanori</creator><creator>Sitia, Giovanni</creator><creator>Iannacone, Matteo</creator><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150423</creationdate><title>Immunosurveillance of the liver by intravascular effector CD8(+) T cells</title><author>Guidotti, Luca G ; Inverso, Donato ; Sironi, Laura ; Di Lucia, Pietro ; Fioravanti, Jessica ; Ganzer, Lucia ; Fiocchi, Amleto ; Vacca, Maurizio ; Aiolfi, Roberto ; Sammicheli, Stefano ; Mainetti, Marta ; Cataudella, Tiziana ; Raimondi, Andrea ; Gonzalez-Aseguinolaza, Gloria ; Protzer, Ulrike ; Ruggeri, Zaverio M ; Chisari, Francis V ; Isogawa, Masanori ; Sitia, Giovanni ; Iannacone, Matteo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-b01af78264f1c997aea982f772d29a19415dac9e11aa328b6abc5479b360b66e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Movement</topic><topic>Endothelial Cells - metabolism</topic><topic>Hepatitis B - immunology</topic><topic>Hepatitis B - pathology</topic><topic>Hepatitis B virus - physiology</topic><topic>Hepatocytes - metabolism</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Liver - cytology</topic><topic>Liver - immunology</topic><topic>Liver Cirrhosis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Monitoring, Immunologic</topic><topic>Platelet Adhesiveness</topic><topic>Specific Pathogen-Free Organisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guidotti, Luca G</creatorcontrib><creatorcontrib>Inverso, Donato</creatorcontrib><creatorcontrib>Sironi, Laura</creatorcontrib><creatorcontrib>Di Lucia, Pietro</creatorcontrib><creatorcontrib>Fioravanti, Jessica</creatorcontrib><creatorcontrib>Ganzer, Lucia</creatorcontrib><creatorcontrib>Fiocchi, Amleto</creatorcontrib><creatorcontrib>Vacca, Maurizio</creatorcontrib><creatorcontrib>Aiolfi, Roberto</creatorcontrib><creatorcontrib>Sammicheli, Stefano</creatorcontrib><creatorcontrib>Mainetti, Marta</creatorcontrib><creatorcontrib>Cataudella, Tiziana</creatorcontrib><creatorcontrib>Raimondi, Andrea</creatorcontrib><creatorcontrib>Gonzalez-Aseguinolaza, Gloria</creatorcontrib><creatorcontrib>Protzer, Ulrike</creatorcontrib><creatorcontrib>Ruggeri, Zaverio M</creatorcontrib><creatorcontrib>Chisari, Francis V</creatorcontrib><creatorcontrib>Isogawa, Masanori</creatorcontrib><creatorcontrib>Sitia, Giovanni</creatorcontrib><creatorcontrib>Iannacone, Matteo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guidotti, Luca G</au><au>Inverso, Donato</au><au>Sironi, Laura</au><au>Di Lucia, Pietro</au><au>Fioravanti, Jessica</au><au>Ganzer, Lucia</au><au>Fiocchi, Amleto</au><au>Vacca, Maurizio</au><au>Aiolfi, Roberto</au><au>Sammicheli, Stefano</au><au>Mainetti, Marta</au><au>Cataudella, Tiziana</au><au>Raimondi, Andrea</au><au>Gonzalez-Aseguinolaza, Gloria</au><au>Protzer, Ulrike</au><au>Ruggeri, Zaverio M</au><au>Chisari, Francis V</au><au>Isogawa, Masanori</au><au>Sitia, Giovanni</au><au>Iannacone, Matteo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunosurveillance of the liver by intravascular effector CD8(+) T cells</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2015-04-23</date><risdate>2015</risdate><volume>161</volume><issue>3</issue><spage>486</spage><epage>500</epage><pages>486-500</pages><issn>0092-8674</issn><issn>1097-4172</issn><eissn>1097-4172</eissn><abstract>Effector CD8(+) T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.</abstract><cop>United States</cop><pmid>25892224</pmid><doi>10.1016/j.cell.2015.03.005</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals CD8-Positive T-Lymphocytes - immunology Cell Movement Endothelial Cells - metabolism Hepatitis B - immunology Hepatitis B - pathology Hepatitis B virus - physiology Hepatocytes - metabolism Hyaluronic Acid - metabolism Liver - cytology Liver - immunology Liver Cirrhosis Mice Mice, Inbred C57BL Monitoring, Immunologic Platelet Adhesiveness Specific Pathogen-Free Organisms |
| title | Immunosurveillance of the liver by intravascular effector CD8(+) T cells |
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