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Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses
Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptide...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473604/ https://www.ncbi.nlm.nih.gov/pubmed/37662376 http://dx.doi.org/10.1101/2023.08.19.553954 |
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author | 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 |
author_facet | 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 |
author_sort | Vecchio, Federica |
collection | PubMed |
description | Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8(+) T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the 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. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8(+) T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination. |
format | Online Article Text |
id | pubmed-10473604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104736042023-09-02 Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses 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 bioRxiv Article Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8(+) T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the 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. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8(+) T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination. Cold Spring Harbor Laboratory 2023-08-21 /pmc/articles/PMC10473604/ /pubmed/37662376 http://dx.doi.org/10.1101/2023.08.19.553954 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article 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 Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title | Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title_full | Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title_fullStr | Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title_full_unstemmed | Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title_short | Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses |
title_sort | coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral cd8+ t-cell responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473604/ https://www.ncbi.nlm.nih.gov/pubmed/37662376 http://dx.doi.org/10.1101/2023.08.19.553954 |
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