Loss of Αβ but Not Γδ T Cells in Chickens Causes a Severe Phenotype.

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 chickens, an important livestock species with a high availability of gamma delta T cells. To investigate the role of gamma delta and alpha beta 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 gamma or beta chain, leading to a complete loss of either gamma delta or alpha beta T cells. Our results show that a deletion of alpha beta T cells but not gamma delta T cells resulted in a severe phenotype in KO chickens. The alpha beta T cell KO chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of alpha beta T cell KO chickens revealed a significant increase in monocytes and expectedly the absence of CD4+ T cells including FoxP3+ regulatory T cells. Surprisingly there was no increase of gamma delta T cells. 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. CRISPR/Cas9 was used to knockout either alpha beta or gamma delta T cells in chickens in order to further analyze the adaptive immune response in poultry. While chickens lacking gamma delta T cells showed no obvious phenotype besides missing gamma delta T cells, birds lacking alpha beta T cells revealed a severe immunophenotype.#image