Unraveling the role of γδ T cells in the pathogenesis of an oncogenic avian herpesvirus

Mohammad Ateih Sabsabi,Ahmed Kheimar,Yu You, Dominik von La Roche,Sonja Härtle,Thomas W. Göbel, Theresa von Heyl,Benjamin Schusser,Benedikt B. Kaufer

biorxiv(2023)

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摘要
Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that causes deadly T cell lymphomas in chickens. MDV is highly cell associated which allows the virus to evade antibody-mediated virus neutralization. Therefore, T cell-mediated immune responses are thought to be crucial for combating this deadly pathogen. In chickens, gamma delta (γδ) T cells represent a major population with up to 50% of all peripheral T cells. However, their role in MDV pathogenesis and tumor formation remains poorly understood. To investigate the role of γδ T cells in MDV pathogenesis, we infected genetically modified chickens that lack γδ T cells (TCR Cγ-/-) 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 increased by up to 89-fold in the thymus and spleen, both potential sites of T cell transformation. Taken together, our data provide the first evidence that γδ T cells play an important role in restricting MDV replication, pathogenesis and tumors caused by this deadly pathogen. ### Competing Interest Statement The authors have declared no competing interest.
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