Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 < sup > + < /sup > T cell responses

Sci Adv. 2024 Mar 8;10(10):eadl1122. doi: 10.1126/sciadv.adl1122. Epub 2024 Mar 6.ABSTRACTCoxsackievirus 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.PMID:38446892 | DOI:10.1126/sciadv.adl1122
Source: Adv Data - Category: Epidemiology Authors: Source Type: research