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Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8+ T cell responses.
Sci. Adv. 10:eadl1122 (2024)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Recent-onset; Type-1; Virus; Risk; Identification; Replication; B1; B3
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
Journal
Science Advances
Quellenangaben
Volume: 10,
Issue: 10,
Article Number: eadl1122
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
Washington, DC [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)
Institute for Pancreatic Beta Cell Research (IPI)
Grants
Leona M. & Harry B. Helmsley Charitable Trust
Swedish Research Council
Swedish Child Diabetes Foundation
Strategic Research Program in Diabetes at Karolinska Institutet
Federal Ministry for Education and Research (BMBF)
National Institutes of Health NIDDK grant
Steve Morgan Foundation Grand Challenge Senior Research Fellowship
Novo Nordisk Postdoctoral Fellowship program at Karolinska Institutet
JDRF Postdoctoral Fellowship
Agence Nationale de la Recherche grant
Fondation pour la Recherche Medicale grant
JDRF
Human Atlas of Neonatal Development and Early Life Immunity program (HANDEL-I)
European Federation of Pharmaceutical Industries and Associations
EU
Innovative Medicines Initiative 2 Joint Undertaking
JDRF nPOD-Virus grant
Swedish Research Council
Swedish Child Diabetes Foundation
Strategic Research Program in Diabetes at Karolinska Institutet
Federal Ministry for Education and Research (BMBF)
National Institutes of Health NIDDK grant
Steve Morgan Foundation Grand Challenge Senior Research Fellowship
Novo Nordisk Postdoctoral Fellowship program at Karolinska Institutet
JDRF Postdoctoral Fellowship
Agence Nationale de la Recherche grant
Fondation pour la Recherche Medicale grant
JDRF
Human Atlas of Neonatal Development and Early Life Immunity program (HANDEL-I)
European Federation of Pharmaceutical Industries and Associations
EU
Innovative Medicines Initiative 2 Joint Undertaking
JDRF nPOD-Virus grant