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Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival.
- Source :
-
Blood [Blood] 2005 Sep 01; Vol. 106 (5), pp. 1726-33. Date of Electronic Publication: 2005 May 12. - Publication Year :
- 2005
-
Abstract
- Intrathymic T-cell maturation critically depends on the selective expansion of thymocytes expressing a functionally rearranged T-cell receptor (TCR) beta chain. In addition, TCR-independent signals also contribute to normal T-cell development. It is unclear whether and how signals from the 2 types of pathways are integrated. Here, we show that T-cell factor-1 (TCF-1), a nuclear effector of the canonical wingless/int (wnt)/catenin signaling pathway, ensures the survival of proliferating, pre-TCR(+) thymocytes. The survival of pre-TCR(+) thymocytes requires the presence of the N-terminal catenin-binding domain in TCF-1. This domain can bind the transcriptional coactivator beta-catenin and may also bind gamma-catenin (plakoglobin). However, in the absence of gamma-catenin, T-cell development is normal, supporting a role for beta-catenin. Signaling competent beta-catenin is present prior to and thus arises independently from pre-TCR signaling and does not substantially increase on pre-TCR signaling. In contrast, pre-TCR signaling significantly induces TCF-1 expression. This coincides with the activation of a wnt/catenin/TCF reporter transgene in vivo. Collectively, these data suggest that efficient TCF-dependent transcription requires that pre-TCR signaling induces TCF-1 expression, whereas wnt signals may provide the coactivator such as beta-catenin. The 2 pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage.
- Subjects :
- Animals
Cell Cycle drug effects
Cell Cycle immunology
Cell Differentiation drug effects
Cell Differentiation immunology
Cell Survival drug effects
Cell Survival immunology
Cytoskeletal Proteins pharmacology
DNA-Binding Proteins deficiency
Desmoplakins
Hepatocyte Nuclear Factor 1-alpha
Homeodomain Proteins immunology
Intercellular Signaling Peptides and Proteins immunology
Lymphoid Enhancer-Binding Factor 1
Mice
Mice, Inbred C57BL
Structure-Activity Relationship
T Cell Transcription Factor 1
Thymus Gland cytology
Thymus Gland immunology
Transcription Factors deficiency
Wnt Proteins
gamma Catenin
DNA-Binding Proteins immunology
Receptors, Antigen, T-Cell immunology
Signal Transduction immunology
T-Lymphocytes immunology
Transcription Factors immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 106
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 15890681
- Full Text :
- https://doi.org/10.1182/blood-2005-01-0337