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
Main Authors: 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
Format: Article
Language:English
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
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Summary: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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adl1122