The role of T cells in the protection against epithelial infections in chickens

T细胞是鸡的主要淋巴细胞群，与哺乳动物的T细胞有许多共同的特征，包括表达αβ或γδ T细胞受体的亚群。与小鼠和人相比，鸡体内γδ T细胞的频率可高达周围淋巴样细胞的50%。初次感染艾美耳球虫可使鸡产生强烈免疫力，接种疫苗的动物可在48至72小时内清除寄生虫；然而，潜在的免疫机制仍然广泛未知。T细胞介导的免疫反应被认为是消除寄生虫的必要条件。上皮内淋巴细胞是肠道中最常见的淋巴样细胞，它们大多表达T细胞特异性抗原。虽然T细胞对控制感染至关重要，但对鸡中促成这种免疫反应的T细胞亚群一无所知。为了解剖鸡体内T细胞介导的免疫应答，我们培育了γδ T细胞敲除鸡，并将培育和表征αβ T细胞敲除鸡。此外，我们将交叉αβ和γδ T细胞敲除鸡，以获得完全敲除T细胞的鸟类。在快速基于ngs的MHC基因分型的帮助下，我们将确定适合过继转移研究的动物，以便在病原体攻击之前转移确定的T细胞群。在不同的T细胞敲除鸡系中使用艾美耳球虫攻击研究，我们将定义T细胞亚群在感染背景下的作用。此外，移植细胞群的命运将通过FACS，免疫组织化学以及单细胞测序分析来跟踪。FOR5130内的各个研究项目受益于彼此之间的合作，并提供了更好地了解鸡的免疫系统与重要病原体的关系。

T cells represent a major lymphocyte population in chickens and share many features with their mammalian counterparts including subsets expressing the αβ or γδ T cell receptors. In contrast to mice and humans the frequency of γδ T cells in chickens can be as high as 50% of the peripheral lymphoid cells. Primary infection with Eimeria leads to the development of a strong immunity in chickens and vaccinated animals clear the parasite within 48 to 72h; however, the underlying immune mechanisms remain widely unknown. T cell mediated immune response are thought to be essential for the elimination of the parasite. Intraepithelial lymphocytes are the most common lymphoid cells in the gut and most of them express T cell specific antigens. While T cells are essential for the control of infection, nothing is known about the T cell subpopulations that contribute to this immune response in chickens. In order to dissect the T cell mediated immune response in chickens we generated γδ T cell knockout chickens and will generate and characterize αβ T cell knockout chickens. In addition, we will cross αβ and γδ T cell knockout chickens to obtain birds with a complete T cell knockout. With the help of rapid NGS-based MHC genotyping we will identify animals suitable for adoptive transfer studies in order to transfer defined T cell populations prior to pathogen challenge. Using Eimeria challenge studies in the different T cell knockout chicken lines, we will define the role of T cell subsets in the context of infection. Furthermore, the fate of transferred cell populations will be followed by FACS, Immunohistochemistry as well as single-cell sequencing analyses. 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.