Coxsackievirus infection induces direct pancreatic ß cell killing but poor antiviral CD8+ T cell responses.
Sci Adv
; 10(10): eadl1122, 2024 Mar 08.
Article
in En
| MEDLINE
| ID: mdl-38446892
ABSTRACT
Coxsackievirus B (CVB) infection of pancreatic ß cells is associated with ß cell autoimmunity and type 1 diabetes. We investigated how CVB affects human ß cells and anti-CVB T cell responses. ß 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 ß cell antigen GAD. Infected ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coxsackievirus Infections
/
Diabetes Mellitus, Type 1
/
Insulin-Secreting Cells
Limits:
Humans
Language:
En
Journal:
Sci Adv
Year:
2024
Type:
Article
Affiliation country:
France