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Article Dans Une Revue Science Advances Année : 2024

Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 + T cell responses

Federica Vecchio
Alexia Carré
Daniil Korenkov
Zhicheng Zhou
Paola Apaolaza
Soile Tuomela
  • Fonction : Auteur
Orlando Burgos-Morales
  • Fonction : Auteur
Isaac Snowhite
Javier Perez-Hernandez
Barbara Brandao
Georgia Afonso
John Kaddis
Sally Kent
  • Fonction : Auteur
Maki Nakayama
Sarah Richardson
Jutta Laiho
Michele Solimena
  • Fonction : Auteur
Zuzana Marinicova
Janine Sanchez
Carmen Bustamante
  • Fonction : Auteur
Patricia Gomez
Soren Buus
Sylvaine You
Alberto Pugliese
Heikki Hyoty
Teresa Rodriguez-Calvo
Malin Flodstrom-Tullberg
Roberto Mallone

Résumé

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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Dates et versions

hal-04542472 , version 1 (11-04-2024)

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Federica Vecchio, Alexia Carré, Daniil Korenkov, Zhicheng Zhou, Paola Apaolaza, et al.. Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 + T cell responses. Science Advances , 2024, 10 (10), pp.eadl1122. ⟨10.1126/sciadv.adl1122⟩. ⟨hal-04542472⟩
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