Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients
Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are st...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-10, Vol.8 (10), p.e78686-e78686 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e78686 |
|---|---|
| container_issue | 10 |
| container_start_page | e78686 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Iancu, Emanuela M Gannon, Philippe O Laurent, Julien Gupta, Bhawna Romero, Pedro Michielin, Olivier Romano, Emanuela Speiser, Daniel E Rufer, Nathalie |
| description | Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution. |
| doi_str_mv | 10.1371/journal.pone.0078686 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1445923140</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_d2eff8ebd5304adc82e1623cdfe6a8e3</doaj_id><sourcerecordid>3110575731</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-8485e91c7f24d47f9c3fc5c11efb6b7b72bed796ac1960633d7bc1fdfb8659673</originalsourceid><addsrcrecordid>eNptks1u1DAUhSMEomXgDRBYYsNmBv_FcTZIZShQqRIsClvLsa-nHiV2sB2kvj2ZTlq1iJUt-7vH91yfqnpN8IawhnzYxykF3W_GGGCDcSOFFE-qU9IyuhYUs6cP9ifVi5z3GNdMCvG8OqGc4pq2_LSafkDKPhcIBlB06PzTL6RD8TsI6zyC8c4btP0s0RUy0PfI9DHEcjNCRnZKPuzQdRwg5qLLDPphmAKgBCaGXHyZio8B-YCMnvUTGmcKQskvq2dO9xleLeuq-vnl_Gr7bX35_evF9uxybWoqylpyWUNLTOMot7xxrWHO1IYQcJ3omq6hHdimFdqQVmDBmG06Q5x1nRR1Kxq2qt4edcc-ZrVMLCvCed1SRjieiYsjYaPeqzH5QacbFbVXtwcx7ZROs7UelKXgnITO1gxzbY2kQARlxjoQWgKbtT4ur03dANbMTpPuH4k-vgn-Wu3iH8Uklmz-nFX1fhFI8fcEuajB58PYdYA43fbdNqLmRM7ou3_Q_7vjR8qkmHMCd98MweqQorsqdUiRWlI0l715aOS-6C427C8XTsi_</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1445923140</pqid></control><display><type>article</type><title>Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Iancu, Emanuela M ; Gannon, Philippe O ; Laurent, Julien ; Gupta, Bhawna ; Romero, Pedro ; Michielin, Olivier ; Romano, Emanuela ; Speiser, Daniel E ; Rufer, Nathalie</creator><creatorcontrib>Iancu, Emanuela M ; Gannon, Philippe O ; Laurent, Julien ; Gupta, Bhawna ; Romero, Pedro ; Michielin, Olivier ; Romano, Emanuela ; Speiser, Daniel E ; Rufer, Nathalie</creatorcontrib><description>Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0078686</identifier><identifier>PMID: 24205294</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Adult ; Aged ; Amino Acid Sequence ; Antigens ; Antigens, Viral - immunology ; Cancer ; CCR5 protein ; CD27 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; Cell Differentiation ; Chemotherapy ; Clone Cells - immunology ; Cytomegalovirus ; Epstein-Barr virus ; Gene expression ; Herpesvirus 4, Human - immunology ; HIV ; Homeostasis ; Homing ; Human immunodeficiency virus ; Humans ; Immune reconstitution ; Immunology ; Infections ; Interleukin 7 receptors ; L-selectin ; Lymphocytes ; Lymphocytes T ; Medical research ; Melanoma ; Melanoma - immunology ; Melanoma - virology ; Memory ; Middle Aged ; Oncology ; Patients ; Priming ; Receptors, Antigen, T-Cell - chemistry ; Receptors, Antigen, T-Cell - metabolism ; T cell receptors ; T-cell receptor ; Time Factors ; Viral infections ; Viruses</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e78686-e78686</ispartof><rights>2013 Iancu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Iancu et al 2013 Iancu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-8485e91c7f24d47f9c3fc5c11efb6b7b72bed796ac1960633d7bc1fdfb8659673</citedby><cites>FETCH-LOGICAL-c526t-8485e91c7f24d47f9c3fc5c11efb6b7b72bed796ac1960633d7bc1fdfb8659673</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/PMC3808305/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808305/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24205294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iancu, Emanuela M</creatorcontrib><creatorcontrib>Gannon, Philippe O</creatorcontrib><creatorcontrib>Laurent, Julien</creatorcontrib><creatorcontrib>Gupta, Bhawna</creatorcontrib><creatorcontrib>Romero, Pedro</creatorcontrib><creatorcontrib>Michielin, Olivier</creatorcontrib><creatorcontrib>Romano, Emanuela</creatorcontrib><creatorcontrib>Speiser, Daniel E</creatorcontrib><creatorcontrib>Rufer, Nathalie</creatorcontrib><title>Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution.</description><subject>Activation</subject><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Antigens</subject><subject>Antigens, Viral - immunology</subject><subject>Cancer</subject><subject>CCR5 protein</subject><subject>CD27 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation</subject><subject>Chemotherapy</subject><subject>Clone Cells - immunology</subject><subject>Cytomegalovirus</subject><subject>Epstein-Barr virus</subject><subject>Gene expression</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>HIV</subject><subject>Homeostasis</subject><subject>Homing</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune reconstitution</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interleukin 7 receptors</subject><subject>L-selectin</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical research</subject><subject>Melanoma</subject><subject>Melanoma - immunology</subject><subject>Melanoma - virology</subject><subject>Memory</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Patients</subject><subject>Priming</subject><subject>Receptors, Antigen, T-Cell - chemistry</subject><subject>Receptors, Antigen, T-Cell - metabolism</subject><subject>T cell receptors</subject><subject>T-cell receptor</subject><subject>Time Factors</subject><subject>Viral infections</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks1u1DAUhSMEomXgDRBYYsNmBv_FcTZIZShQqRIsClvLsa-nHiV2sB2kvj2ZTlq1iJUt-7vH91yfqnpN8IawhnzYxykF3W_GGGCDcSOFFE-qU9IyuhYUs6cP9ifVi5z3GNdMCvG8OqGc4pq2_LSafkDKPhcIBlB06PzTL6RD8TsI6zyC8c4btP0s0RUy0PfI9DHEcjNCRnZKPuzQdRwg5qLLDPphmAKgBCaGXHyZio8B-YCMnvUTGmcKQskvq2dO9xleLeuq-vnl_Gr7bX35_evF9uxybWoqylpyWUNLTOMot7xxrWHO1IYQcJ3omq6hHdimFdqQVmDBmG06Q5x1nRR1Kxq2qt4edcc-ZrVMLCvCed1SRjieiYsjYaPeqzH5QacbFbVXtwcx7ZROs7UelKXgnITO1gxzbY2kQARlxjoQWgKbtT4ur03dANbMTpPuH4k-vgn-Wu3iH8Uklmz-nFX1fhFI8fcEuajB58PYdYA43fbdNqLmRM7ou3_Q_7vjR8qkmHMCd98MweqQorsqdUiRWlI0l715aOS-6C427C8XTsi_</recordid><startdate>20131025</startdate><enddate>20131025</enddate><creator>Iancu, Emanuela M</creator><creator>Gannon, Philippe O</creator><creator>Laurent, Julien</creator><creator>Gupta, Bhawna</creator><creator>Romero, Pedro</creator><creator>Michielin, Olivier</creator><creator>Romano, Emanuela</creator><creator>Speiser, Daniel E</creator><creator>Rufer, Nathalie</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131025</creationdate><title>Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients</title><author>Iancu, Emanuela M ; Gannon, Philippe O ; Laurent, Julien ; Gupta, Bhawna ; Romero, Pedro ; Michielin, Olivier ; Romano, Emanuela ; Speiser, Daniel E ; Rufer, Nathalie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-8485e91c7f24d47f9c3fc5c11efb6b7b72bed796ac1960633d7bc1fdfb8659673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Activation</topic><topic>Adult</topic><topic>Aged</topic><topic>Amino Acid Sequence</topic><topic>Antigens</topic><topic>Antigens, Viral - immunology</topic><topic>Cancer</topic><topic>CCR5 protein</topic><topic>CD27 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation</topic><topic>Chemotherapy</topic><topic>Clone Cells - immunology</topic><topic>Cytomegalovirus</topic><topic>Epstein-Barr virus</topic><topic>Gene expression</topic><topic>Herpesvirus 4, Human - immunology</topic><topic>HIV</topic><topic>Homeostasis</topic><topic>Homing</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune reconstitution</topic><topic>Immunology</topic><topic>Infections</topic><topic>Interleukin 7 receptors</topic><topic>L-selectin</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical research</topic><topic>Melanoma</topic><topic>Melanoma - immunology</topic><topic>Melanoma - virology</topic><topic>Memory</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Patients</topic><topic>Priming</topic><topic>Receptors, Antigen, T-Cell - chemistry</topic><topic>Receptors, Antigen, T-Cell - metabolism</topic><topic>T cell receptors</topic><topic>T-cell receptor</topic><topic>Time Factors</topic><topic>Viral infections</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iancu, Emanuela M</creatorcontrib><creatorcontrib>Gannon, Philippe O</creatorcontrib><creatorcontrib>Laurent, Julien</creatorcontrib><creatorcontrib>Gupta, Bhawna</creatorcontrib><creatorcontrib>Romero, Pedro</creatorcontrib><creatorcontrib>Michielin, Olivier</creatorcontrib><creatorcontrib>Romano, Emanuela</creatorcontrib><creatorcontrib>Speiser, Daniel E</creatorcontrib><creatorcontrib>Rufer, Nathalie</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iancu, Emanuela M</au><au>Gannon, Philippe O</au><au>Laurent, Julien</au><au>Gupta, Bhawna</au><au>Romero, Pedro</au><au>Michielin, Olivier</au><au>Romano, Emanuela</au><au>Speiser, Daniel E</au><au>Rufer, Nathalie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-25</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e78686</spage><epage>e78686</epage><pages>e78686-e78686</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24205294</pmid><doi>10.1371/journal.pone.0078686</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-10, Vol.8 (10), p.e78686-e78686 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1445923140 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Activation Adult Aged Amino Acid Sequence Antigens Antigens, Viral - immunology Cancer CCR5 protein CD27 antigen CD8 antigen CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology Cell Differentiation Chemotherapy Clone Cells - immunology Cytomegalovirus Epstein-Barr virus Gene expression Herpesvirus 4, Human - immunology HIV Homeostasis Homing Human immunodeficiency virus Humans Immune reconstitution Immunology Infections Interleukin 7 receptors L-selectin Lymphocytes Lymphocytes T Medical research Melanoma Melanoma - immunology Melanoma - virology Memory Middle Aged Oncology Patients Priming Receptors, Antigen, T-Cell - chemistry Receptors, Antigen, T-Cell - metabolism T cell receptors T-cell receptor Time Factors Viral infections Viruses |
| title | Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T17%3A34%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Persistence%20of%20EBV%20antigen-specific%20CD8%20T%20cell%20clonotypes%20during%20homeostatic%20immune%20reconstitution%20in%20cancer%20patients&rft.jtitle=PloS%20one&rft.au=Iancu,%20Emanuela%20M&rft.date=2013-10-25&rft.volume=8&rft.issue=10&rft.spage=e78686&rft.epage=e78686&rft.pages=e78686-e78686&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0078686&rft_dat=%3Cproquest_plos_%3E3110575731%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1445923140&rft_id=info:pmid/24205294&rft_doaj_id=oai_doaj_org_article_d2eff8ebd5304adc82e1623cdfe6a8e3&rfr_iscdi=true |