Enforced Expression of GATA-3 During T Cell Development Inhibits Maturation of CD8 Single-Positive Cells and Induces Thymic Lymphoma in Transgenic Mice

The zinc finger transcription factor GATA-3 is of critical importance for early T cell development and commitment of Th2 cells. To study the role of GATA-3 in early T cell development, we analyzed and modified GATA-3 expression in vivo. In mice carrying a targeted insertion of a lacZ reporter on one...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-07, Vol.167 (2), p.715-723
Main Authors: Nawijn, Martijn C, Ferreira, Rita, Dingjan, Gemma M, Kahre, Olev, Drabek, Dubravka, Karis, Alar, Grosveld, Frank, Hendriks, Rudolf W
Format: Article
Language:English
Subjects:
Animals
CD2 Antigens - genetics
CD8 antigen
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Lineage - genetics
Cell Lineage - immunology
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Down-Regulation - genetics
Down-Regulation - immunology
GATA-3 protein
GATA3 Transcription Factor
Gene Expression Regulation - immunology
Growth Inhibitors - antagonists & inhibitors
Growth Inhibitors - biosynthesis
Growth Inhibitors - genetics
Growth Inhibitors - physiology
Humans
Locus Control Region - immunology
Lymph Nodes - pathology
Lymphoma, T-Cell - etiology
Lymphoma, T-Cell - immunology
Lymphoma, T-Cell - pathology
Lymphopenia - genetics
Lymphopenia - immunology
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Spleen - pathology
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocyte Subsets - pathology
Thymus Neoplasms - etiology
Thymus Neoplasms - immunology
Thymus Neoplasms - pathology
Trans-Activators - antagonists & inhibitors
Trans-Activators - biosynthesis
Trans-Activators - genetics
Trans-Activators - physiology
Transgenes - immunology
Up-Regulation - genetics
Up-Regulation - immunology
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Summary:The zinc finger transcription factor GATA-3 is of critical importance for early T cell development and commitment of Th2 cells. To study the role of GATA-3 in early T cell development, we analyzed and modified GATA-3 expression in vivo. In mice carrying a targeted insertion of a lacZ reporter on one allele, we found that GATA-3 transcription in CD4(+)CD8(+) double-positive thymocytes correlated with the onset of positive selection events, i.e., TCRalphabeta up-regulation and CD69 expression. LacZ expression remained high ( approximately 80% of cells) during maturation of CD4 single-positive (SP) cells in the thymus, but in developing CD8 SP cells the fraction of lacZ-expressing cells decreased to
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.2.715