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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.


Journal article


J Immunol

Publication Date





2888 - 2894


3T3 Cells, Animals, CD4 Antigens, CD8 Antigens, 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