Loss of αβ but not γδ Tcells in chickens causes a severe phenotype.

Abstract

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