Knockout of αβ but not γδ T cells in chickens is associated with high cytotoxicity and deficiency of regulatory and helper T cells

Abstract

The availability of genetically modified mice has facilitated the study of mammalian T cells. No model has yet been developed to study these cells in chicken, an important livestock species with a high availability of gd T cells. To investigate the role of gd and ab T cell populations in birds, we generated chickens lacking these T cell populations. This was achieved by genomic deletion of the constant region of the T cell receptor g or b chain, leading to a complete loss of either gd or ab T cells. Our results show that a deletion of ab T cells but not gd T cells resulted in a severe phenotype in knockout chickens. The ab T cell knockout chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of ab T cell knockout chickens revealed a significant increase in monocytes and the absence of CD4+ T cells and FoxP3+ regulatory T cells compared to wild type chickens. In addition, we observed a significant decrease in immunoglobulins, B lymphocytes, and changes in the bursa morphology. Our data reveal the consequences of T cell knockouts in chickens and provide new insights into their function in vertebrates.