Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells
A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8+ T cell responses. However, in many situations, including persistent virusinfection, specific T cell responses are rarely detected using this technology. This raises the question of whether s...
Gespeichert in:
Veröffentlicht in: | European journal of immunology 2004-06, Vol.34 (6), p.1570-1577 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1577 |
---|---|
container_issue | 6 |
container_start_page | 1570 |
container_title | European journal of immunology |
container_volume | 34 |
creator | Barnes, Eleanor Ward, Scott M. Kasprowicz, Victoria O. Dusheiko, Geoffrey Klenerman, Paul Lucas, Michaela |
description | A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8+ T cell responses. However, in many situations, including persistent virusinfection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are ‘deleted’ (or ‘exhausted’) or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8+ T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti‐PE‐labeled magnetic beads to enrich tetramer‐positive HCV‐specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV‐specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV‐specific responses at frequencies of >0.0011% of CD8+ T cells (∼1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus‐specific CD8+ T cells during chronic virus infection and is readily transferable to the study of other viral, self‐ or tumor‐specific T cells. |
doi_str_mv | 10.1002/eji.200424898 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71961765</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71961765</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3378-bc0dd2f4318ce0f14026e0900a7c445a8e3e70680d703f666dc23d0456fe94553</originalsourceid><addsrcrecordid>eNp9kLFOwzAQhi0EoqUwsiJPLCjl7DhOMqJSoAiJBebIdS6SkZsEOynq1oEH4Bn7JLhqRTemO-m--_TrJ-SSwZgB8Fv8MGMOILjI8uyIDFnCWSSYYMdkCMBExPMMBuTM-w8AyGWSn5IBS5jkgssh6d9t59Rm_eOx9qYzS6TaKu836-8Z7TDcFuioqpVdeeOpwyUq62kbFtP03q5oX5fYoe7U3CJtm7a3qjNN7WlThb9gNE5ZOrnPbuhbsGq01p-Tkypo8GI_R-T9Yfo2eYpeXh9nk7uXSMdxmkVzDWXJKxGzTCNUTACXCDmASrUQicowxhRkBmUKcSWlLDWPSxCJrDAXSRKPyPXO27rms0ffFQvjtwlUjSF9kbJcslRuwWgHatd477AqWmcWyq0KBsW25yL0XPz1HPirvbifL7A80PtiA5DugC9jcfW_rZg-zw7qX4ytjUk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71961765</pqid></control><display><type>article</type><title>Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells</title><source>Wiley-Blackwell Journals</source><source>Wiley-Blackwell Open Access Backfiles</source><source>MEDLINE</source><source>Free E-Journal (出版社公開部分のみ)</source><creator>Barnes, Eleanor ; Ward, Scott M. ; Kasprowicz, Victoria O. ; Dusheiko, Geoffrey ; Klenerman, Paul ; Lucas, Michaela</creator><creatorcontrib>Barnes, Eleanor ; Ward, Scott M. ; Kasprowicz, Victoria O. ; Dusheiko, Geoffrey ; Klenerman, Paul ; Lucas, Michaela</creatorcontrib><description>A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8+ T cell responses. However, in many situations, including persistent virusinfection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are ‘deleted’ (or ‘exhausted’) or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8+ T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti‐PE‐labeled magnetic beads to enrich tetramer‐positive HCV‐specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV‐specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV‐specific responses at frequencies of >0.0011% of CD8+ T cells (∼1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus‐specific CD8+ T cells during chronic virus infection and is readily transferable to the study of other viral, self‐ or tumor‐specific T cells.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200424898</identifier><identifier>PMID: 15162426</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag</publisher><subject>Antigens, Neoplasm ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - virology ; Hepacivirus - immunology ; Hepatitis C Antigens - immunology ; Hepatitis C Antigens - isolation & purification ; Hepatitis C, Chronic - immunology ; Hepatitis C, Chronic - virology ; HLA-A2 Antigen - immunology ; Human ; Humans ; Immunomagnetic Separation - methods ; MART-1 Antigen ; Neoplasm Proteins - immunology ; Phycoerythrin - immunology ; T lymphocytes ; Virus</subject><ispartof>European journal of immunology, 2004-06, Vol.34 (6), p.1570-1577</ispartof><rights>Copyright © 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3378-bc0dd2f4318ce0f14026e0900a7c445a8e3e70680d703f666dc23d0456fe94553</citedby><cites>FETCH-LOGICAL-c3378-bc0dd2f4318ce0f14026e0900a7c445a8e3e70680d703f666dc23d0456fe94553</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%2Feji.200424898$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.200424898$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15162426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barnes, Eleanor</creatorcontrib><creatorcontrib>Ward, Scott M.</creatorcontrib><creatorcontrib>Kasprowicz, Victoria O.</creatorcontrib><creatorcontrib>Dusheiko, Geoffrey</creatorcontrib><creatorcontrib>Klenerman, Paul</creatorcontrib><creatorcontrib>Lucas, Michaela</creatorcontrib><title>Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8+ T cell responses. However, in many situations, including persistent virusinfection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are ‘deleted’ (or ‘exhausted’) or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8+ T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti‐PE‐labeled magnetic beads to enrich tetramer‐positive HCV‐specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV‐specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV‐specific responses at frequencies of >0.0011% of CD8+ T cells (∼1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus‐specific CD8+ T cells during chronic virus infection and is readily transferable to the study of other viral, self‐ or tumor‐specific T cells.</description><subject>Antigens, Neoplasm</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - virology</subject><subject>Hepacivirus - immunology</subject><subject>Hepatitis C Antigens - immunology</subject><subject>Hepatitis C Antigens - isolation & purification</subject><subject>Hepatitis C, Chronic - immunology</subject><subject>Hepatitis C, Chronic - virology</subject><subject>HLA-A2 Antigen - immunology</subject><subject>Human</subject><subject>Humans</subject><subject>Immunomagnetic Separation - methods</subject><subject>MART-1 Antigen</subject><subject>Neoplasm Proteins - immunology</subject><subject>Phycoerythrin - immunology</subject><subject>T lymphocytes</subject><subject>Virus</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLFOwzAQhi0EoqUwsiJPLCjl7DhOMqJSoAiJBebIdS6SkZsEOynq1oEH4Bn7JLhqRTemO-m--_TrJ-SSwZgB8Fv8MGMOILjI8uyIDFnCWSSYYMdkCMBExPMMBuTM-w8AyGWSn5IBS5jkgssh6d9t59Rm_eOx9qYzS6TaKu836-8Z7TDcFuioqpVdeeOpwyUq62kbFtP03q5oX5fYoe7U3CJtm7a3qjNN7WlThb9gNE5ZOrnPbuhbsGq01p-Tkypo8GI_R-T9Yfo2eYpeXh9nk7uXSMdxmkVzDWXJKxGzTCNUTACXCDmASrUQicowxhRkBmUKcSWlLDWPSxCJrDAXSRKPyPXO27rms0ffFQvjtwlUjSF9kbJcslRuwWgHatd477AqWmcWyq0KBsW25yL0XPz1HPirvbifL7A80PtiA5DugC9jcfW_rZg-zw7qX4ytjUk</recordid><startdate>200406</startdate><enddate>200406</enddate><creator>Barnes, Eleanor</creator><creator>Ward, Scott M.</creator><creator>Kasprowicz, Victoria O.</creator><creator>Dusheiko, Geoffrey</creator><creator>Klenerman, Paul</creator><creator>Lucas, Michaela</creator><general>WILEY‐VCH Verlag</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>7X8</scope></search><sort><creationdate>200406</creationdate><title>Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells</title><author>Barnes, Eleanor ; Ward, Scott M. ; Kasprowicz, Victoria O. ; Dusheiko, Geoffrey ; Klenerman, Paul ; Lucas, Michaela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3378-bc0dd2f4318ce0f14026e0900a7c445a8e3e70680d703f666dc23d0456fe94553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antigens, Neoplasm</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - virology</topic><topic>Hepacivirus - immunology</topic><topic>Hepatitis C Antigens - immunology</topic><topic>Hepatitis C Antigens - isolation & purification</topic><topic>Hepatitis C, Chronic - immunology</topic><topic>Hepatitis C, Chronic - virology</topic><topic>HLA-A2 Antigen - immunology</topic><topic>Human</topic><topic>Humans</topic><topic>Immunomagnetic Separation - methods</topic><topic>MART-1 Antigen</topic><topic>Neoplasm Proteins - immunology</topic><topic>Phycoerythrin - immunology</topic><topic>T lymphocytes</topic><topic>Virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barnes, Eleanor</creatorcontrib><creatorcontrib>Ward, Scott M.</creatorcontrib><creatorcontrib>Kasprowicz, Victoria O.</creatorcontrib><creatorcontrib>Dusheiko, Geoffrey</creatorcontrib><creatorcontrib>Klenerman, Paul</creatorcontrib><creatorcontrib>Lucas, Michaela</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><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barnes, Eleanor</au><au>Ward, Scott M.</au><au>Kasprowicz, Victoria O.</au><au>Dusheiko, Geoffrey</au><au>Klenerman, Paul</au><au>Lucas, Michaela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2004-06</date><risdate>2004</risdate><volume>34</volume><issue>6</issue><spage>1570</spage><epage>1577</epage><pages>1570-1577</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8+ T cell responses. However, in many situations, including persistent virusinfection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are ‘deleted’ (or ‘exhausted’) or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8+ T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti‐PE‐labeled magnetic beads to enrich tetramer‐positive HCV‐specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV‐specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV‐specific responses at frequencies of >0.0011% of CD8+ T cells (∼1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus‐specific CD8+ T cells during chronic virus infection and is readily transferable to the study of other viral, self‐ or tumor‐specific T cells.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag</pub><pmid>15162426</pmid><doi>10.1002/eji.200424898</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0014-2980 |
ispartof | European journal of immunology, 2004-06, Vol.34 (6), p.1570-1577 |
issn | 0014-2980 1521-4141 |
language | eng |
recordid | cdi_proquest_miscellaneous_71961765 |
source | Wiley-Blackwell Journals; Wiley-Blackwell Open Access Backfiles; MEDLINE; Free E-Journal (出版社公開部分のみ) |
subjects | Antigens, Neoplasm CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - virology Hepacivirus - immunology Hepatitis C Antigens - immunology Hepatitis C Antigens - isolation & purification Hepatitis C, Chronic - immunology Hepatitis C, Chronic - virology HLA-A2 Antigen - immunology Human Humans Immunomagnetic Separation - methods MART-1 Antigen Neoplasm Proteins - immunology Phycoerythrin - immunology T lymphocytes Virus |
title | Ultra‐sensitive class I tetramer analysis reveals previously undetectable populations of antiviral 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=2024-12-24T06%3A35%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ultra%E2%80%90sensitive%20class%E2%80%84I%20tetramer%20analysis%20reveals%20previously%20undetectable%20populations%20of%20antiviral%20CD8+%20T%E2%80%84cells&rft.jtitle=European%20journal%20of%20immunology&rft.au=Barnes,%20Eleanor&rft.date=2004-06&rft.volume=34&rft.issue=6&rft.spage=1570&rft.epage=1577&rft.pages=1570-1577&rft.issn=0014-2980&rft.eissn=1521-4141&rft_id=info:doi/10.1002/eji.200424898&rft_dat=%3Cproquest_cross%3E71961765%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=71961765&rft_id=info:pmid/15162426&rfr_iscdi=true |