揭示 γδ T 细胞在致癌禽疱疹病毒发病机制中的作用。
Unraveling the role of γδ T cells in the pathogenesis of an oncogenic avian herpesvirus.
发表日期:2024 Jul 02
作者:
Mohammad A Sabsabi, Ahmed Kheimar, Yu You, Dominik von La Roche, Sonja Härtle, Thomas W Göbel, Theresa von Heyl, Benjamin Schusser, Benedikt B Kaufer
来源:
mBio
摘要:
马立克氏病病毒 (MDV) 是一种致癌性α疱疹病毒,可导致鸡致命的淋巴瘤。在鸡中,高达 50% 的外周 T 细胞是 γδ (γδ) T 细胞。迄今为止,它们在 MDV 发病机制和肿瘤形成中的作用仍知之甚少。为了研究 γδ T 细胞在 MDV 发病机制中的作用,我们用高毒力的 MDV 感染了最近产生的 γδ T 细胞敲除鸡。引人注目的是,在缺乏 γδ T 细胞的情况下,疾病和肿瘤的发病率大幅增加,这表明 γδ T 细胞在针对 MDV 的免疫反应中发挥着重要作用。在缺乏 γδ T 细胞的情况下,病毒在胸腺和脾脏中的复制急剧增加,而胸腺和脾脏是 T 细胞转化的潜在位点。综上所述,我们的数据提供了第一个证据,证明 γδ T 细胞在这种高致癌性疱疹病毒的发病机制和肿瘤形成中发挥着重要作用。 重要性 γδ (γδ) T 细胞是鸡中最丰富的 T 细胞,但它们在对抗病原体仍然知之甚少。马立克氏病病毒 (MDV) 是一种重要的兽医病原体,可引起动物最常见的癌症之一,并被用作病毒诱导肿瘤形成的模型。我们的研究表明,γδ T 细胞在对抗 MDV 中发挥着至关重要的作用,因为如果没有这些细胞,疾病和肿瘤的发病率就会急剧增加。 γδ T 细胞限制病毒在关键淋巴器官中的复制,从而降低引起肿瘤和疾病的可能性。这项研究为 γδ T 细胞在这种高度致癌病毒的发病机制中的作用提供了新的见解。
Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that causes deadly lymphomas in chickens. In chickens, up to 50% of all peripheral T cells are gamma delta (γδ) T cells. Until now, their role in MDV pathogenesis and tumor formation remains poorly understood. To investigate the role of γδ T cells in MDV pathogenesis, we infected recently generated γδ T cell knockout chickens with very virulent MDV. Strikingly, disease and tumor incidence were highly increased in the absence of γδ T cells, indicating that γδ T cells play an important role in the immune response against MDV. In the absence of γδ T cells, virus replication was drastically increased in the thymus and spleen, which are potential sites of T cell transformation. Taken together, our data provide the first evidence that γδ T cells play an important role in the pathogenesis and tumor formation of this highly oncogenic herpesvirus.IMPORTANCEGamma delta (γδ) T cells are the most abundant T cells in chickens, but their role in fighting pathogens remains poorly understood. Marek's disease virus (MDV) is an important veterinary pathogen, that causes one of the most frequent cancers in animals and is used as a model for virus-induced tumor formation. Our study revealed that γδ T cells play a crucial role in combating MDV, as disease and tumor incidence drastically increased in the absence of these cells. γδ T cells restricted virus replication in the key lymphoid organs, thereby decreasing the likelihood of causing tumors and disease. This study provides novel insights into the role of γδ T cells in the pathogenesis of this highly oncogenic virus.