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

Federica Vecchio (1) , Alexia Carré (1) , Daniil Korenkov (1) , Zhicheng Zhou (1) , Paola Apaolaza , Soile Tuomela , Orlando Burgos-Morales , Isaac Snowhite , Javier Perez-Hernandez , Barbara Brandao , Georgia Afonso , Clémentine Halliez (1, 2) , John Kaddis , Sally Kent , Maki Nakayama , Sarah Richardson , Joelle Vinh (3, 4) , Yann Verdier (3) , Jutta Laiho , Raphael Scharfmann (1) , Michele Solimena , Zuzana Marinicova , Elise Bismuth (5) , Nadine Lucidarme (6) , Janine Sanchez , Carmen Bustamante , Patricia Gomez , Soren Buus , Sylvaine You (1) , Alberto Pugliese , Heikki Hyoty , Teresa Rodriguez-Calvo , Malin Flodstrom-Tullberg , Roberto Mallone

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 Service de diabétologie [CHU Cochin]
3 PdC - Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249)
4 SMBP - Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032)
5 Hôpital Robert Debré
6 Hôpital Jean Verdier [AP-HP]

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.

Domaines: Maladies infectieuses; Immunité adaptative; Endocrinologie et métabolisme

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⟩