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

T 细胞在预防鸡上皮感染中的作用

• 批准号: 453662189
• 负责人: Professor Dr. Benjamin Schusser
• 金额: --
• 依托单位: Professur für Biotechnologie der Reproduktion
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/453662189?language=en
• 关键词: role; cells; protection; against; epithelial

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.

T细胞是鸡的主要淋巴细胞群，与哺乳动物T细胞有许多共同的特征，包括表达αβ或γδT细胞受体的亚群。与小鼠和人相比，鸡的γδT细胞的频率可以高达外周淋巴样细胞的50%。初次感染艾美耳球虫可使鸡产生较强的免疫力，接种疫苗的动物可在48至72小时内清除该寄生虫；然而，其潜在的免疫机制仍不清楚。T细胞介导的免疫反应被认为是消灭寄生虫的关键。上皮内淋巴细胞是肠道中最常见的淋巴样细胞，大多数表达T细胞特异性抗原。虽然T细胞对于控制感染是必不可少的，但对鸡的这种免疫反应的T细胞亚群知之甚少。为了解剖鸡T细胞介导的免疫应答，我们建立了γδT细胞基因敲除鸡，并将产生和鉴定αβT细胞基因敲除鸡。此外，我们还将与αβ和γδT细胞敲除鸡杂交，以获得T细胞完全敲除的鸡。在基于NGS的MHC快速基因分型的帮助下，我们将确定适合进行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。利用艾美耳球虫在不同T细胞敲除鸡系中的挑战研究，我们将确定T细胞亚群在感染环境中的作用。此外，转移细胞群体的命运将通过流式细胞仪、免疫组织化学以及单细胞测序分析来跟踪。FOR5130中的个别研究项目受益于彼此之间的合作，并提供了对鸡与重要病原体相关的免疫系统的更好了解。