SEPARATELY EXPRESSED T-CELL RECEPTOR-ALPHA AND BETA-CHAIN TRANSGENES EXERT OPPOSITE EFFECTS ON T-CELL DIFFERENTIATION AND NEOPLASTIC TRANSFORMATION

Two aspects of T cell differentiation in T cell receptor (TCR)-transge nic mice, the generation of an unusual population of CD4(-)CD8(-)TCR(d ivided by) thymocytes and the absence of gamma delta cells, have been the focus of extensive investigation. To examine the basis for these p henomena, we investigated the effects of separate expression of a tran sgenic TCR alpha chain and a transgenic TCR beta chain on thymocyte di fferentiation. Our data indicate that expression of a transgenic TCR a lpha chain causes thymocytes to differentiate into a CD4(-)CD8(-)TCR() lineage at an early developmental stage, depleting the number of thy mocytes that differentiate into the alpha beta lineage. Surprisingly, expression of the TCR alpha chain transgene is also associated with th e development of T cell lymphosarcoma. In contrast, expression of the transgenic TCR beta chain causes immature T cells to accelerate differ entiation into the alpha beta lineage and thus inhibits the generation of gamma delta cells. Our observations provide a model for understand ing T cell differentiation in TCR-transgenic mice.