REDUNDANT REGULATION OF T-CELL DIFFERENTIATION AND TCR-ALPHA GENE-EXPRESSION BY THE TRANSCRIPTION FACTORS LEF-1 AND TCF-1

Lymphoid enhancer factor 1 (LEF-1) and T cell factor 1 (TCF-1) are clo sely related transcription factors that are both expressed during muri ne T cell differentiation and that regulate the T cell receptor alpha (TCR alpha) enhancer in transfection assays. Targeted gene disruption of either the Tcf1 or Lef1 gene in mice did not affect TCR alpha gene expression and resulted in an incomplete defect or no defect in thymoc yte differentiation. Here, we examine a potential redundancy of these transcription factors by analyzing double-mutant mice. In fetal thymic organ cultures from Lef1(-/-)Tcf1(-/-)mice, alpha/beta T cell differe ntiation is completely arrested at the immature CD8(+) single-positive (CD8(+) ISP) stage and is markedly impaired at an earlier stage. In a ddition, we find that sorted CD8(+) ISP cells from Lef1(-/-)Tcf1(-/-) mice express TCR beta but show a severely reduced level of TCR alpha g ene transcription. Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differentiation and gene express ion.