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ZAP-70 is a Syk family tyrosine kinase that plays an essential role in initiating TCR signals. Deficiency in ZAP-70 causes a defect in the development at CD4+CD8+ thymocytes due to defective TCR-mediated positive and negative selection. Using a newly devised retrovirus gene transfer and an efficient green fluorescence protein detection technique in fetal thymus organ cultures, the present study shows that forced expression in developing thymocytes of a catalytically inactive mutant of ZAP-70, but not wild-type ZAP-70, inhibits T cell development at the earlier CD4-CD8- stage. The ZAP-70 mutant blocked the generation of CD4+CD8+ thymocytes even in the absence of endogenous ZAP-70. Thus, the present results demonstrate a novel technique for gene transfer into developing T cells and suggest that ZAP-70/Syk family tyrosine kinases are involved in the signals inducing the generation of CD4+CD8+ thymocytes.

Type

Journal article

Journal

J Immunol

Publication Date

15/09/1998

Volume

161

Pages

2888 - 2894

Keywords

3T3 Cells, Animals, Antigens, CD4, Antigens, CD8, Cell Differentiation, Enzyme Activation, Fetus, Gene Transfer Techniques, Genetic Vectors, Green Fluorescent Proteins, Growth Inhibitors, Luminescent Proteins, Mice, Mice, Knockout, Mutagenesis, Protein-Tyrosine Kinases, Retroviridae, T-Lymphocyte Subsets, ZAP-70 Protein-Tyrosine Kinase