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Repression of hedgehog signal transduction in T-lineage cells increases TCR-induced activation and proliferation.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2008 Apr 01; Vol. 7 (7), pp. 904-8. Date of Electronic Publication: 2008 Jan 18. - Publication Year :
- 2008
-
Abstract
- Hedgehog proteins signal for differentiation, survival and proliferation of the earliest thymocyte progenitors, but their functions at later stages of thymocyte development and in peripheral T-cell function are controversial. Here we show that repression of Hedgehog (Hh) pathway activation in T-lineage cells, by expression of a transgenic repressor form of Gli2 (Gli2DeltaC2), increased T-cell differentiation and activation in response to TCR signalling. Expression of the Gli2DeltaC2 transgene increased differentiation from CD4(+)CD8(+) to single positive thymocyte, and increased peripheral T cell populations. Gli2DeltaC2 T-cells were hyper-responsive to activation by ligation of CD3 and CD28: they expressed cell surface activation markers CD69 and CD25 more quickly, and proliferated more than wild-type T-cells. These data show that Hedgehog pathway activation in thymocytes and T-cells negatively regulates TCR-dependent differentiation and proliferation. Thus, as negative regulators of TCR-dependent events, Hh proteins provide an environmental influence on T-cell fate.
- Subjects :
- Animals
DNA Primers genetics
Genotype
Kruppel-Like Transcription Factors metabolism
Mice
Mice, Transgenic
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction genetics
Zinc Finger Protein Gli2
Cell Differentiation immunology
Hedgehog Proteins metabolism
Signal Transduction physiology
T-Lymphocytes cytology
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 7
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 18414059
- Full Text :
- https://doi.org/10.4161/cc.7.7.5628