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ARD:B细胞耗竭以I型干扰素依赖性方式损害疫苗接种诱导的CD8+ T细胞反应

2021-12-27 MedSci原创 MedSci原创

根据不同刺激,B细胞可以调节CD8+ T细胞反应。因此,B细胞耗竭导致从头抗体反应的缺乏并影响包括细胞毒性T细胞在内的细胞反应的功效。必须重新评估为B细胞耗竭患者选择合适的接种疫苗。

     目的:单克隆抗CD20抗体利妥昔单抗经常用于治疗淋巴瘤和自身免疫性疾病,能有效清除循环B细胞。相应地,在感染或疫苗接种期间,B细胞耗尽的患者几乎不会产生从头抗体反应。因此,B细胞耗竭患者的有效免疫反应在很大程度上取决于保护性T细胞反应。

     方法:在利妥昔单抗治疗的类风湿性关节炎(RA)患者和B细胞缺陷小鼠中研究了 CD8+ T细胞扩增,这些小鼠接种/感染了不同的疫苗/病原体。

     结果:与健康对照相比,接受了利妥昔单抗治疗的RA患者接种了Influvac疫苗后,流感特异性CD8+ T细胞的扩增减少。此外,与野生型小鼠相比,感染了小鼠适应型流感或改良痘苗病毒安卡拉的B细胞缺陷型JHT小鼠表现出病毒特异性CD8+ T细胞的扩增减少。值得注意的是,JHT小鼠没有CD8+ T细胞扩增的内在损伤,因为在JHT和野生型小鼠中,痘苗病毒感染诱导了类似的T细胞扩增。B细胞的直接I型干扰素受体信号传导对于诱导B细胞中的几种趋化因子和通过增强MHC-I的表达来支持T细胞帮助是必要的。

      结论:根据不同刺激,B细胞可以调节CD8+ T细胞反应。因此,B细胞耗竭导致从头抗体反应的缺乏并影响包括细胞毒性T细胞在内的细胞反应的功效。必须重新评估为B细胞耗竭患者选择合适的接种疫苗,以有效诱导保护性CD8+ T细胞反应。 

出处:Graalmann T, Borst K, Manchanda H, et al. B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner. Annals of the Rheumatic Diseases 2021;80:1537-1544.

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    2021-12-30 飘渺星辰
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