Role of T cell subsets in Marek’s disease virus pathogenesis

马立克氏病病毒（MDV）是一种高度致癌的α疱疹病毒，感染鸡并导致麻痹，免疫抑制和致命的淋巴瘤。MDV诱导的淋巴瘤被认为是动物中最常见的临床诊断癌症，并且该病毒在全球家禽业中造成了巨大的经济损失。在易感鸡中，MDV感染可导致高达100%的死亡率，这取决于宿主的遗传背景和病毒株的毒力。尽管目前的MDV疫苗在最大限度地减少由于肿瘤形成而造成的商业损失方面非常有效，但它们不会引起杀菌免疫，从而使MDV毒株在接种疫苗的鸡中继续进化。自从广泛接种疫苗以来，MDV田间毒株的毒力不断增加。这些毒性更强的毒株能够克服疫苗保护，对家禽生产构成严重威胁。因此，我们需要更好地了解MDV的发病机制和疫苗反应，以开发更有效的疫苗来控制这种致命的病原体。尽管多年的研究，T细胞亚群在MDV发病机制和疫苗保护中的作用仍然知之甚少，主要是由于缺乏鸡的反向遗传学。工作包6（WP6）的目的是i）确定γδ T细胞在MDV感染中的作用，ii）评估它们是否对疫苗保护重要，iii）研究MDV发病机制是否依赖于αβ T细胞的存在。为了实现这些目标，我们将使用αβ和γδ T细胞敲除鸡结合分子和免疫学方法。该实验不仅将揭示这些T细胞亚群在MDV发病机制和疫苗保护中的作用，而且还将扩大对这种高致癌性病毒的生命周期的认识。FOR5130内的各个研究项目将受益于彼此之间的合作，并提供更好地了解鸡的免疫系统与重要病原体的关系。

Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes paralysis, immunosuppression and deadly lymphomas. MDV-induced lymphomas are considered to be the most prevalent clinically-diagnosed cancer in animals and the virus causes substantial economic losses in poultry industry worldwide. In susceptible chickens, MDV infection can cause mortality of up to 100%, depending on the genetic background of the host and the virulence of the virus strain. Even though current MDV vaccines are highly effective in minimizing commercial losses due to tumor formation, they do not elicit sterilizing immunity, allowing a continued evolution of MDV strains in vaccinated chickens. Since the advent of widespread vaccination, there has been a continuous increase in the virulence of MDV field strains. These more virulent strains are able to overcome vaccine protection and pose a serious threat to poultry production. Therefore, we need a better understanding of MDV pathogenesis and vaccine responses in chickens to develop more potent vaccines that control this deadly pathogen.Despite many years of research, the role of T cell subsets in MDV pathogenesis and vaccine protection remains poorly understood, mostly due to the lack of reverse genetics in chickens. The aim of work package 6 (WP6) is i) to determine the role of γδ T cells in MDV infection, ii) to assess if they are important for vaccine protection and iii) to investigate if MDV pathogenesis is dependent on the presence of αβ T cells. To address these aims, we will use αβ and γδ T cell knockout chickens in combination with molecular and immunological methods. The proposed experiments will not only shed light on the role of these T cell subsets in MDV pathogenesis and vaccine protection but also expand the knowledge on the life cycle of this highly oncogenic virus.The individual research projects within FOR5130 benefit from the collaborations among each other and provide a better insight into the immune system of chickens in relation to important pathogens.