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Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 + T cell responses
Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and...
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| Published in: | Science advances 2024-03, Vol.10 (10), p.eadl1122 |
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| creator | Vecchio, Federica Carré, Alexia Korenkov, Daniil Zhou, Zhicheng Apaolaza, Paola Tuomela, Soile Burgos-Morales, Orlando Snowhite, Isaac Perez-Hernandez, Javier Brandao, Barbara Afonso, Georgia Halliez, Clémentine Kaddis, John Kent, Sally C Nakayama, Maki Richardson, Sarah J Vinh, Joelle Verdier, Yann Laiho, Jutta Scharfmann, Raphael Solimena, Michele Marinicova, Zuzana Bismuth, Elise Lucidarme, Nadine Sanchez, Janine Bustamante, Carmen Gomez, Patricia Buus, Soren You, Sylvaine Pugliese, Alberto Hyoty, Heikki Rodriguez-Calvo, Teresa Flodstrom-Tullberg, Malin Mallone, Roberto |
| description | Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8
T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8
T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8
T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination. |
| doi_str_mv | 10.1126/sciadv.adl1122 |
| format | article |
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T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8
T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8
T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adl1122</identifier><identifier>PMID: 38446892</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science (AAAS)</publisher><subject>Adaptive immunology ; Antibodies ; Antiviral Agents ; Biomedicine and Life Sciences ; CD8-Positive T-Lymphocytes ; Coxsackievirus Infections ; Diabetes Mellitus, Type 1 ; Endocrinology and metabolism ; Epitopes ; Human health and pathology ; Humans ; Immunology ; Infectious diseases ; Insulin-Secreting Cells ; Life Sciences ; Medicin och hälsovetenskap ; Peptides ; SciAdv r-articles ; Virology</subject><ispartof>Science advances, 2024-03, Vol.10 (10), p.eadl1122</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. 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We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8
T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8
T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8
T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.</description><subject>Adaptive immunology</subject><subject>Antibodies</subject><subject>Antiviral Agents</subject><subject>Biomedicine and Life Sciences</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Coxsackievirus Infections</subject><subject>Diabetes Mellitus, Type 1</subject><subject>Endocrinology and metabolism</subject><subject>Epitopes</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infectious diseases</subject><subject>Insulin-Secreting Cells</subject><subject>Life Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Peptides</subject><subject>SciAdv 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Isaac</au><au>Perez-Hernandez, Javier</au><au>Brandao, Barbara</au><au>Afonso, Georgia</au><au>Halliez, Clémentine</au><au>Kaddis, John</au><au>Kent, Sally C</au><au>Nakayama, Maki</au><au>Richardson, Sarah J</au><au>Vinh, Joelle</au><au>Verdier, Yann</au><au>Laiho, Jutta</au><au>Scharfmann, Raphael</au><au>Solimena, Michele</au><au>Marinicova, Zuzana</au><au>Bismuth, Elise</au><au>Lucidarme, Nadine</au><au>Sanchez, Janine</au><au>Bustamante, Carmen</au><au>Gomez, Patricia</au><au>Buus, Soren</au><au>You, Sylvaine</au><au>Pugliese, Alberto</au><au>Hyoty, Heikki</au><au>Rodriguez-Calvo, Teresa</au><au>Flodstrom-Tullberg, Malin</au><au>Mallone, Roberto</au><aucorp>nPOD-Virus Working Group</aucorp><aucorp>the nPOD-Virus Working Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 + T cell responses</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2024-03-08</date><risdate>2024</risdate><volume>10</volume><issue>10</issue><spage>eadl1122</spage><pages>eadl1122-</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8
T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8
T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8
T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science (AAAS)</pub><pmid>38446892</pmid><doi>10.1126/sciadv.adl1122</doi><orcidid>https://orcid.org/0000-0001-8144-7194</orcidid><orcidid>https://orcid.org/0000-0003-0370-4145</orcidid><orcidid>https://orcid.org/0000-0003-3790-6140</orcidid><orcidid>https://orcid.org/0000-0002-3211-7647</orcidid><orcidid>https://orcid.org/0000-0003-1531-8583</orcidid><orcidid>https://orcid.org/0000-0003-3759-7317</orcidid><orcidid>https://orcid.org/0000-0001-8363-1999</orcidid><orcidid>https://orcid.org/0000-0002-9846-8861</orcidid><orcidid>https://orcid.org/0000-0003-2685-2052</orcidid><orcidid>https://orcid.org/0000-0001-8321-778X</orcidid><orcidid>https://orcid.org/0000-0002-6752-7670</orcidid><orcidid>https://orcid.org/0009-0008-6416-8247</orcidid><orcidid>https://orcid.org/0000-0002-1578-5205</orcidid><orcidid>https://orcid.org/0000-0002-1160-6062</orcidid><orcidid>https://orcid.org/0009-0008-0128-0100</orcidid><orcidid>https://orcid.org/0000-0002-3319-0053</orcidid><orcidid>https://orcid.org/0000-0002-0009-3687</orcidid><orcidid>https://orcid.org/0000-0001-9712-2917</orcidid><orcidid>https://orcid.org/0000-0002-5683-515X</orcidid><orcidid>https://orcid.org/0000-0002-5443-4651</orcidid><orcidid>https://orcid.org/0000-0003-4607-8818</orcidid><orcidid>https://orcid.org/0000-0002-7550-054X</orcidid><orcidid>https://orcid.org/0009-0008-9387-0318</orcidid><orcidid>https://orcid.org/0000-0001-9137-7951</orcidid><orcidid>https://orcid.org/0000-0002-7211-0319</orcidid><orcidid>https://orcid.org/0000-0001-7184-2668</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2375-2548 |
| ispartof | Science advances, 2024-03, Vol.10 (10), p.eadl1122 |
| issn | 2375-2548 2375-2548 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_850300 |
| source | American Association for the Advancement of Science; PubMed Central |
| subjects | Adaptive immunology Antibodies Antiviral Agents Biomedicine and Life Sciences CD8-Positive T-Lymphocytes Coxsackievirus Infections Diabetes Mellitus, Type 1 Endocrinology and metabolism Epitopes Human health and pathology Humans Immunology Infectious diseases Insulin-Secreting Cells Life Sciences Medicin och hälsovetenskap Peptides SciAdv r-articles Virology |
| title | Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 + T cell responses |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T15%3A32%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Coxsackievirus%20infection%20induces%20direct%20pancreatic%20%CE%B2%20cell%20killing%20but%20poor%20antiviral%20CD8%20+%20T%20cell%20responses&rft.jtitle=Science%20advances&rft.au=Vecchio,%20Federica&rft.aucorp=nPOD-Virus%20Working%20Group&rft.date=2024-03-08&rft.volume=10&rft.issue=10&rft.spage=eadl1122&rft.pages=eadl1122-&rft.issn=2375-2548&rft.eissn=2375-2548&rft_id=info:doi/10.1126/sciadv.adl1122&rft_dat=%3Cproquest_swepu%3E2942187392%3C/proquest_swepu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c513t-accdb0f4255b2f51a050de88c9afa2f601490066694d1a6055f8f66de304c8a53%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2942187392&rft_id=info:pmid/38446892&rfr_iscdi=true |