Redundant regulation of T cell differentiation and TCRα gene expression by the transcription factors LEF-1 and TCF-1

Ross M. Okamura, Mikael Sigvardsson, Juan Galceran, Sjef Verbeek, Hans Clevers, Rudolf Grosschedl

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

284 Citaten (Scopus)

Samenvatting

Lymphoid enhancer factor 1 (LEF-1) and T cell factor 1 (TCF-1) are closely related transcription factors that are both expressed during murine T cell differentiation and that regulate the T cell receptor α (TCRα) enhancer in transfection assays. Targeted gene disruption of either the Tcf1 or Lef1 gene in mice did not affect TCRα germ expression and resulted in an incomplete defect or no defect in thymocyte 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, α/β T cell differentiation is completely arrested at the immature CD8+ single-positive (CD8+ ISP) stage and is markedly impaired at an earlier stage. In addition, we find that sorted CD8+ ISP cells from Lef1(-/-)Tcf1(- /-) mice express TCRβ but show a severely reduced level of TCRα gene transcription. Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differentiation and gene expression.

Originele taal-2Engels
Pagina's (van-tot)11-20
Aantal pagina's10
TijdschriftImmunity
Volume8
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan. 1998
Extern gepubliceerdJa

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