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Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Mar 01; Vol. 170 (5), pp. 2356-66. - Publication Year :
- 2003
-
Abstract
- T cell differentiation in the thymus is dependent upon signaling through the TCR and is characterized by the resulting changes in expression patterns of CD4 and CD8 surface coreceptor molecules. Although recent studies have characterized the effects of proximal TCR signaling on T cell differentiation, the downstream integration of these signals remains largely unknown. The growth factor independence-1 (GFI1) and GFI1B transcriptional repressors may regulate cytokine signaling pathways to affect lymphocyte growth and survival. In this study, we show that Gfi1 expression is induced upon induction of the T cell program. Gfi1B expression is low and dynamic during T cell development, but is terminated in mature thymocytes. Transgenic expression of GFI1 and GFI1B in T cells allowed us to determine the functional consequences of constitutive expression. GFI1 potentiates response to TCR stimulation and IL-2, whereas GFI1B-transgenic T cells are defective in T cell activation. Moreover, GFI1B-transgenic thymocytes display reduced expression of the late-activation marker IL-7R alpha, and a decrease in CD4(-)8(+) single-positive T cells that can be mitigated by transgenic expression of BCL2 or GFI1. These data show that GFI1 and GFI1B are functionally unique, and implicate a role for GFI1 in the integration of activation and survival signals.
- Subjects :
- Animals
Autoantigens physiology
CD3 Complex immunology
CD3 Complex metabolism
CD4 Antigens biosynthesis
CD8 Antigens biosynthesis
Cell Differentiation genetics
Cell Differentiation immunology
Cell Lineage genetics
Cell Lineage immunology
Cross-Linking Reagents metabolism
DNA-Binding Proteins biosynthesis
DNA-Binding Proteins genetics
Female
Gene Expression Regulation immunology
Genes, MHC Class I immunology
H-Y Antigen biosynthesis
H-Y Antigen genetics
Interleukin-2 pharmacology
Lymphopenia genetics
Lymphopenia immunology
Lymphopoiesis genetics
Lymphopoiesis immunology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 physiology
Receptors, Antigen, T-Cell, alpha-beta physiology
Receptors, Interleukin-7 antagonists & inhibitors
Receptors, Interleukin-7 genetics
Repressor Proteins genetics
T-Lymphocyte Subsets metabolism
Thymus Gland cytology
Thymus Gland immunology
Thymus Gland metabolism
Transgenes immunology
Proto-Oncogene Proteins biosynthesis
Receptors, Interleukin-7 biosynthesis
Repressor Proteins biosynthesis
T-Lymphocyte Subsets cytology
T-Lymphocyte Subsets immunology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12594258
- Full Text :
- https://doi.org/10.4049/jimmunol.170.5.2356