Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes
The Rockefeller University Press, 1999
academicJournal
Zugriff:
Differentiation of human T cells into T helper (Th)1 and Th2 cells is vital for the development of cell-mediated and humoral immunity, respectively. However, the precise mechanism responsible for the Th1 cell differentiation is not fully clarified. We have studied the expression and function of Txk, a member of the Tec family of nonreceptor tyrosine kinases. We found that Txk expression is restricted to Th1/Th0 cells with IFN-γ producing potential. Txk transfection of Jurkat T cells resulted in a several-fold increase of IFN-γ mRNA expression and protein production; interleukin (IL)-2 and IL-4 production were unaffected. Antisense oligodeoxynucleotide of Txk specifically inhibited IFN-γ production of normal peripheral blood lymphocytes, antigen-specific Th1 clones, and Th0 clones; IL-2 and IL-4 production by the T cells was unaffected. Txk cotransfection led to the enhanced luciferase activity of plasmid (p)IFN-γ promoter/enhancer (pIFN-γ[-538])-luciferase–transfected Jurkat cells upon mitogen activation. Txk transfection did not affect IL-2 and IL-4 promoter activities. Thus, Txk specifically upregulates IFN-γ gene transcription. In fact, Txk translocated from cytoplasm into nuclei upon activation and transfection with a mutant Txk expression plasmid that lacked a nuclear localization signal sequence did not enhance IFN-γ production by the cells, indicating that nuclear localization of Txk is obligatory for the enhanced IFN-γ production. In addition, IL-12 treatment of peripheral blood CD4+ T cells enhanced the Txk expression, whereas IL-4 treatment completely inhibited it. These results indicate that Txk expression is intimately associated with development of Th1/Th0 cells and is significantly involved in the IFN-γ production by the cells through Th1 cell–specific positive transcriptional regulation of the IFN-γ gene.
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Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes
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Autor/in / Beteiligte Person: | Kashiwakura, Jun-ichi ; Suzuki, Noboru ; Nagafuchi, Hiroko ; Takeno, Mitsuhiro ; Takeba, Yuko ; Shimoyama, Yoshihiro ; Sakane, Tsuyoshi |
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Veröffentlichung: | The Rockefeller University Press, 1999 |
Medientyp: | academicJournal |
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