Project Details
Projekt
Analyzing Avian T Cell Development and Function during Infection: Insights from Chicken TCR Knockout Models
Applicant
Dr. Theresa von Heyl zu Herrnsheim
Subject Area
Veterinary Medical Science
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 434524639
Alpha ß and gamma delta T cells are central components of the avian adaptive immune system and play a crucial role in the defense against pathogens such as Marek's disease virus (MDV) and low pathogenic avian influenza virus (LPAIV). To improve the protection against these diseases in chickens, it is important to better understand the specific functions of these T cell subpopulations. By using state-of-the-art CRISPR/Cas9-mediated gene knockout technology, we aim to assess the distinct roles of alpha ß- and gamma delta-T cells in the immune defense and thus gain important insights into their contribution to adaptive immunity. The importance of the ß-chain of T cell receptor in chickens lies not only in the formation of T cell receptor (TCR), but also in its essential role in thymic development through the formation of a pre-TCR. Therefore, deletion of the ß-chain results in a severe phenotype in chickens. We hypothesize that knocking out the alpha-chain of the TCR results in healthy knockout chickens that completely lack alpha ß-T cells. To answer this question, we generate TCR Cα-knockout chickens and characterize them phenotypically to decipher the difference between alpha- and ß-chain knockout and enable detailed analysis of the alpha ß T cells in chickens. The newly generated TCR C alpha-KO chickens will then be used to study the function of alpha ß T cells in MDV infection. Avian influenza, a highly mutagenic viral infection in birds, leads to significant economic losses and has a high zoonotic potential. Previous studies have shown that gamma delta T cells in mice play a central role in the immune response against influenza A viruses. However, the role of gamma delta T cells in influenza infections in the natural host, the chicken, remains unclear. To investigate the immune response and survival of birds lacking gamma delta T cells, we will infect TCR Cγ KO chickens with LPAIV compared to wild type chickens. Furthermore, adoptive transfer of primed mCherry+ gamma delta T cells into TCR Cγ KO chickens that are subsequently infected with LPAIV will determine the role of gamma delta T cells in immunity against LPAIV. The proposed experiments will specify the importance of the different TCR chains for the development of the chicken immune system. In addition, we will elucidate the role of alpha ß T cells in MDV infection and the function of gamma delta T cells in the context of low pathogenic avian influenza.
DFG Programme
Research Units
