Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses.
Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses.
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柯萨奇病毒感染诱导直接胰腺β细胞杀伤，但抗病毒CD8 T细胞反应较差。
DOI：
10.1101/2023.08.19.553954
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Na
中科院分区：
文献类型：
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作者：
Vecchio,Federica;Carré,Alexia;Korenkov,Daniil;Zhou,Zhicheng;Apaolaza,Paola;Tuomela,Soile;Burgos-Morales,Orlando;Snowhite,Isaac;Perez-Hernandez,Javier;Brandao,Barbara;Afonso,Georgia;Halliez,Clémentine;Kaddis,John;Kent,SallyC;Na
柯萨奇病毒B （CVB）感染胰腺β细胞与β细胞自身免疫和1型糖尿病相关。我们研究了CVB如何影响人β细胞和抗CVB T细胞反应。体外培养的β细胞被CVB有效感染，下调人白细胞抗原（HLA） I类，并呈现少量精选的HLA结合病毒肽。来自cvb血清阳性个体的循环CD8+T细胞识别了这些肽的一部分；只有另一部分被表达衰竭标志物PD-1的效应/记忆T细胞靶向。识别CVB表位的T细胞与β细胞抗原GAD发生交叉反应。被感染的β细胞形成丝状足以传播感染，CVB比CVB反应性T细胞更有效地杀死β细胞。我们的体外和离体数据强调了CD8+T细胞对CVB的有限反应，支持了CVB疫苗预防1型糖尿病试验的基本原理。识别结构和非结构CVB表位的CD8+T细胞提供了生物标志物来区分感染和疫苗接种的反应。
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.