缺乏天然杀手T细胞的猪对流感的细胞反应发生了改变
Taeyong Kwon1, Weihong Gu2,3, Igor Morozov1
1Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
自然杀伤性T (NKT) 细胞在流感免疫中起着双重作用,在感染后抑制T细胞扩张,但有助于疫苗反应. 缺乏NKT细胞的猪表现出改变的免疫动力学,突出显示了它们在流感中的恒温功能.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 传染性疾病 传染性疾病
背景情况:
- 天生的T细胞,包括天然杀手T (NKT) 细胞,在流感感染和疫苗接种期间调节适应性免疫力至关重要.
- 这些细胞释放细胞因子,影响病毒特异性T和B细胞反应和抗体产生的大小和范围.
研究的目的:
- 用转化猪模型研究NKT细胞对抗流感A病毒免疫反应的特定贡献.
- 阐明NKT细胞在免疫反应的不同阶段,从感染到接种疫苗中的作用.
主要方法:
- 使用了感染猪流感病毒H3N2的CD1D表达 (NKT-完好无损) 和CD1D缺陷 (NKT缺陷) 的猪.
- 经过先前的粘膜免疫接种或不使用经过修改的活疫苗感染后评估的免疫反应.
- 采用单细胞αβT细胞受体 (TCR) 和B细胞受体 (BCR) 测序,并描述了肺的γδ TCR谱.
主要成果:
- 接种疫苗在NKT完整和NKT缺乏的猪中同样降低了病毒载量和肺病理.
- 病毒特异性T细胞在感染后的扩张在NKT缺乏的猪中显著增加,这表明NKT细胞抑制了扩张.
- NKT细胞缺乏导致T细胞在气道周围的缩减少,T和B细胞克隆扩张增加,并改变了γδ TCR谱系动态.
结论:
- NKT细胞在流感免疫反应中表现出平静作用,影响T细胞扩张和收缩动态.
- NKT细胞似乎具有相反的作用,在感染后抑制T细胞扩张,同时可能支持疫苗诱导的免疫力.
- 猪作为一种有价值的翻译模型,用于研究人类流感A感染中的NKT细胞功能.
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