Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells
The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to a...
Gespeichert in:
| Veröffentlicht in: | PLoS pathogens 2011-05, Vol.7 (5), p.e1002045-e1002045 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1002045 |
|---|---|
| container_issue | 5 |
| container_start_page | e1002045 |
| container_title | PLoS pathogens |
| container_volume | 7 |
| creator | Schlaphoff, Verena Lunemann, Sebastian Suneetha, Pothakamuri Venkata Jaroszewicz, Jerzy Grabowski, Jan Dietz, Julia Helfritz, Fabian Bektas, Hueseyin Sarrazin, Christoph Manns, Michael Peter Cornberg, Markus Wedemeyer, Heiner |
| description | The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control. |
| doi_str_mv | 10.1371/journal.ppat.1002045 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1289083305</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A258916212</galeid><doaj_id>oai_doaj_org_article_2834350100cf463fa8f1f03781eda727</doaj_id><sourcerecordid>A258916212</sourcerecordid><originalsourceid>FETCH-LOGICAL-c592t-4fc9e293fc1765b5cc61c140458760d8d61494a94b098f401937fc1701f237f03</originalsourceid><addsrcrecordid>eNptkl1v0zAUhiMEYmPwDxBY4gIQSvHxR-LcII0U2MQEN4Nb4zp25yqNg50g8e9x2nRa0eQLW_bzvufDJ8ueA14ALeH9xo-hU-2i79WwAIwJZvxBdgqc07ykJXt453ySPYlxgzEDCsXj7IRAQTgX1Wn2azmqFtmx04PzHfIWDTcGffuKtGlbFIw2_eADIh8ZelMvCWNvket2TDDrsVUH1UX9M4-90c46jeqleIeudxbxafbIqjaaZ_N-lv34_Om6vsivvn-5rM-vcs0rMuTM6sqQiloNZcFXXOsCNLBUkygL3IimAFYxVbEVroRlGCpaTiwGS9IJ07Ps5d63b32Uc3OiBCIqLCjFPBGXe6LxaiP74LYq_JVeObm78GEtVRicbo0kgjLKceqqtqygVgkLKUYpwDSqJGXy-jBHG1db02jTDUG1R6bHL527kWv_R9KUPqE0GbyeDYL_PZo4yK2LU8NUZ_wYpSgqXgLwIpGv_iPvL26m1irl7zrrU1g9ecpzkn46fTiQRC3uodJqzNZp3xnr0v2RgO0FOvgYg7G3JQKW0xgekpHTGMp5DJPsxd323IoOc0f_AU-91FQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1289083305</pqid></control><display><type>article</type><title>Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Schlaphoff, Verena ; Lunemann, Sebastian ; Suneetha, Pothakamuri Venkata ; Jaroszewicz, Jerzy ; Grabowski, Jan ; Dietz, Julia ; Helfritz, Fabian ; Bektas, Hueseyin ; Sarrazin, Christoph ; Manns, Michael Peter ; Cornberg, Markus ; Wedemeyer, Heiner</creator><creatorcontrib>Schlaphoff, Verena ; Lunemann, Sebastian ; Suneetha, Pothakamuri Venkata ; Jaroszewicz, Jerzy ; Grabowski, Jan ; Dietz, Julia ; Helfritz, Fabian ; Bektas, Hueseyin ; Sarrazin, Christoph ; Manns, Michael Peter ; Cornberg, Markus ; Wedemeyer, Heiner</creatorcontrib><description>The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1002045</identifier><identifier>PMID: 21625589</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antigens, CD - biosynthesis ; Antigens, CD - genetics ; Antigens, CD - immunology ; Biology ; Biomarkers ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Proliferation ; Cells, Cultured ; Gene Expression ; Genetic regulation ; Hepacivirus - immunology ; Hepacivirus - metabolism ; Hepatitis ; Hepatitis C, Chronic - immunology ; Humans ; Immune system ; Infections ; Killer cells ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Lymphocyte Activation - immunology ; Medicine ; Membrane proteins ; Physiological aspects ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Programmed Cell Death 1 Receptor - immunology ; Proteins ; Receptors, Immunologic - biosynthesis ; Receptors, Immunologic - genetics ; Receptors, Immunologic - immunology ; Signaling Lymphocytic Activation Molecule Family ; T cells ; Viral infections</subject><ispartof>PLoS pathogens, 2011-05, Vol.7 (5), p.e1002045-e1002045</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Schlaphoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Schlaphoff V, Lunemann S, Suneetha PV, Jaroszewicz J, Grabowski J, et al. (2011) Dual Function of the NK Cell Receptor 2B4 (CD244) in the Regulation of HCV-Specific CD8+ T Cells. PLoS Pathog 7(5): e1002045. doi:10.1371/journal.ppat.1002045</rights><rights>Schlaphoff et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-4fc9e293fc1765b5cc61c140458760d8d61494a94b098f401937fc1701f237f03</citedby><cites>FETCH-LOGICAL-c592t-4fc9e293fc1765b5cc61c140458760d8d61494a94b098f401937fc1701f237f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21625589$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schlaphoff, Verena</creatorcontrib><creatorcontrib>Lunemann, Sebastian</creatorcontrib><creatorcontrib>Suneetha, Pothakamuri Venkata</creatorcontrib><creatorcontrib>Jaroszewicz, Jerzy</creatorcontrib><creatorcontrib>Grabowski, Jan</creatorcontrib><creatorcontrib>Dietz, Julia</creatorcontrib><creatorcontrib>Helfritz, Fabian</creatorcontrib><creatorcontrib>Bektas, Hueseyin</creatorcontrib><creatorcontrib>Sarrazin, Christoph</creatorcontrib><creatorcontrib>Manns, Michael Peter</creatorcontrib><creatorcontrib>Cornberg, Markus</creatorcontrib><creatorcontrib>Wedemeyer, Heiner</creatorcontrib><title>Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.</description><subject>Antigens, CD - biosynthesis</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - immunology</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Gene Expression</subject><subject>Genetic regulation</subject><subject>Hepacivirus - immunology</subject><subject>Hepacivirus - metabolism</subject><subject>Hepatitis</subject><subject>Hepatitis C, Chronic - immunology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infections</subject><subject>Killer cells</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Lymphocyte Activation - immunology</subject><subject>Medicine</subject><subject>Membrane proteins</subject><subject>Physiological aspects</subject><subject>Programmed Cell Death 1 Receptor - antagonists & inhibitors</subject><subject>Programmed Cell Death 1 Receptor - immunology</subject><subject>Proteins</subject><subject>Receptors, Immunologic - biosynthesis</subject><subject>Receptors, Immunologic - genetics</subject><subject>Receptors, Immunologic - immunology</subject><subject>Signaling Lymphocytic Activation Molecule Family</subject><subject>T cells</subject><subject>Viral infections</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkl1v0zAUhiMEYmPwDxBY4gIQSvHxR-LcII0U2MQEN4Nb4zp25yqNg50g8e9x2nRa0eQLW_bzvufDJ8ueA14ALeH9xo-hU-2i79WwAIwJZvxBdgqc07ykJXt453ySPYlxgzEDCsXj7IRAQTgX1Wn2azmqFtmx04PzHfIWDTcGffuKtGlbFIw2_eADIh8ZelMvCWNvket2TDDrsVUH1UX9M4-90c46jeqleIeudxbxafbIqjaaZ_N-lv34_Om6vsivvn-5rM-vcs0rMuTM6sqQiloNZcFXXOsCNLBUkygL3IimAFYxVbEVroRlGCpaTiwGS9IJ07Ps5d63b32Uc3OiBCIqLCjFPBGXe6LxaiP74LYq_JVeObm78GEtVRicbo0kgjLKceqqtqygVgkLKUYpwDSqJGXy-jBHG1db02jTDUG1R6bHL527kWv_R9KUPqE0GbyeDYL_PZo4yK2LU8NUZ_wYpSgqXgLwIpGv_iPvL26m1irl7zrrU1g9ecpzkn46fTiQRC3uodJqzNZp3xnr0v2RgO0FOvgYg7G3JQKW0xgekpHTGMp5DJPsxd323IoOc0f_AU-91FQ</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Schlaphoff, Verena</creator><creator>Lunemann, Sebastian</creator><creator>Suneetha, Pothakamuri Venkata</creator><creator>Jaroszewicz, Jerzy</creator><creator>Grabowski, Jan</creator><creator>Dietz, Julia</creator><creator>Helfritz, Fabian</creator><creator>Bektas, Hueseyin</creator><creator>Sarrazin, Christoph</creator><creator>Manns, Michael Peter</creator><creator>Cornberg, Markus</creator><creator>Wedemeyer, Heiner</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110501</creationdate><title>Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells</title><author>Schlaphoff, Verena ; Lunemann, Sebastian ; Suneetha, Pothakamuri Venkata ; Jaroszewicz, Jerzy ; Grabowski, Jan ; Dietz, Julia ; Helfritz, Fabian ; Bektas, Hueseyin ; Sarrazin, Christoph ; Manns, Michael Peter ; Cornberg, Markus ; Wedemeyer, Heiner</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-4fc9e293fc1765b5cc61c140458760d8d61494a94b098f401937fc1701f237f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antigens, CD - biosynthesis</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - immunology</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Gene Expression</topic><topic>Genetic regulation</topic><topic>Hepacivirus - immunology</topic><topic>Hepacivirus - metabolism</topic><topic>Hepatitis</topic><topic>Hepatitis C, Chronic - immunology</topic><topic>Humans</topic><topic>Immune system</topic><topic>Infections</topic><topic>Killer cells</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Lymphocyte Activation - immunology</topic><topic>Medicine</topic><topic>Membrane proteins</topic><topic>Physiological aspects</topic><topic>Programmed Cell Death 1 Receptor - antagonists & inhibitors</topic><topic>Programmed Cell Death 1 Receptor - immunology</topic><topic>Proteins</topic><topic>Receptors, Immunologic - biosynthesis</topic><topic>Receptors, Immunologic - genetics</topic><topic>Receptors, Immunologic - immunology</topic><topic>Signaling Lymphocytic Activation Molecule Family</topic><topic>T cells</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schlaphoff, Verena</creatorcontrib><creatorcontrib>Lunemann, Sebastian</creatorcontrib><creatorcontrib>Suneetha, Pothakamuri Venkata</creatorcontrib><creatorcontrib>Jaroszewicz, Jerzy</creatorcontrib><creatorcontrib>Grabowski, Jan</creatorcontrib><creatorcontrib>Dietz, Julia</creatorcontrib><creatorcontrib>Helfritz, Fabian</creatorcontrib><creatorcontrib>Bektas, Hueseyin</creatorcontrib><creatorcontrib>Sarrazin, Christoph</creatorcontrib><creatorcontrib>Manns, Michael Peter</creatorcontrib><creatorcontrib>Cornberg, Markus</creatorcontrib><creatorcontrib>Wedemeyer, Heiner</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schlaphoff, Verena</au><au>Lunemann, Sebastian</au><au>Suneetha, Pothakamuri Venkata</au><au>Jaroszewicz, Jerzy</au><au>Grabowski, Jan</au><au>Dietz, Julia</au><au>Helfritz, Fabian</au><au>Bektas, Hueseyin</au><au>Sarrazin, Christoph</au><au>Manns, Michael Peter</au><au>Cornberg, Markus</au><au>Wedemeyer, Heiner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>7</volume><issue>5</issue><spage>e1002045</spage><epage>e1002045</epage><pages>e1002045-e1002045</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21625589</pmid><doi>10.1371/journal.ppat.1002045</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2011-05, Vol.7 (5), p.e1002045-e1002045 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_1289083305 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Antigens, CD - biosynthesis Antigens, CD - genetics Antigens, CD - immunology Biology Biomarkers CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Proliferation Cells, Cultured Gene Expression Genetic regulation Hepacivirus - immunology Hepacivirus - metabolism Hepatitis Hepatitis C, Chronic - immunology Humans Immune system Infections Killer cells Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Lymphocyte Activation - immunology Medicine Membrane proteins Physiological aspects Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - immunology Proteins Receptors, Immunologic - biosynthesis Receptors, Immunologic - genetics Receptors, Immunologic - immunology Signaling Lymphocytic Activation Molecule Family T cells Viral infections |
| title | Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T12%3A03%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dual%20function%20of%20the%20NK%20cell%20receptor%202B4%20(CD244)%20in%20the%20regulation%20of%20HCV-specific%20CD8+%20T%20cells&rft.jtitle=PLoS%20pathogens&rft.au=Schlaphoff,%20Verena&rft.date=2011-05-01&rft.volume=7&rft.issue=5&rft.spage=e1002045&rft.epage=e1002045&rft.pages=e1002045-e1002045&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1002045&rft_dat=%3Cgale_plos_%3EA258916212%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289083305&rft_id=info:pmid/21625589&rft_galeid=A258916212&rft_doaj_id=oai_doaj_org_article_2834350100cf463fa8f1f03781eda727&rfr_iscdi=true |