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Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses.

Federica VecchioAlexia CarréDaniil KorenkovZhicheng ZhouPaola ApaolazaSoile TuomelaOrlando Burgos-MoralesIsaac SnowhiteJavier Perez-HernandezBarbara BrandaoGeorgia AfonsoClémentine HalliezJohn KaddisSally C KentMaki NakayamaSarah J RichardsonJoelle VinhYann VerdierJutta LaihoRaphael ScharfmannMichele SolimenaZuzana MarinicovaElise BismuthNadine LucidarmeJanine SanchezCarmen BustamantePatricia GomezSoren Buusnull nullSylvaine YouAlberto PuglieseHeikki HyötyTeresa Rodriguez-CalvoMalin Flodström TullbergRoberto Mallone
Published in: bioRxiv : the preprint server for biology (2023)
Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro , downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8 + T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the 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. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8 + T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.
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