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

Abstract 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. Author Summary 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, 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 was 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.