Separately expressed T cell receptor α and β chain transgenes exert opposite effects on T cell differentiation and neoplastic transformation

Two aspects of T cell differentiation in T cell receptor (TCR)-transgenic mice, the generation of an unusual population of CD4^?CD8^?TCR⁺ thymocytes and the absence of γδ cells, have been the focus of extensive investigation. To examine the basis for these phenomena, we investigated the effects of separate expression of a transgenic TCR α chain and a transgenic TCR β chain on thymocyte differentiation. Our data indicate that expression of a transgenic TCR α chain causes thymocytes to differentiate into a CD4^?CD8^?TCR⁺ lineage at an early developmental stage, depleting the number of thymocytes that differentiate into the αβ lineage. Surprisingly, expression of the TCR α chain transgene is also associated with the development of T cell lymphosarcoma. In contrast, expression of the transgenic TCR β chain causes immature T cells to accelerate differentiation into the αβ lineage and thus inhibits the generation of γδ cells. Our observations provide a model for understanding T cell differentiation in TCR-transgenic mice.