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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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
Descripción
Sumario: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.