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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Veröffentlicht in: | Science advances 2024-03, Vol.10 (10), p.eadl1122 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 2375-2548 2375-2548 |
DOI: | 10.1126/sciadv.adl1122 |