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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18 October 1999
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October 18 1999
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
Jun-ichi Kashiwakura,
Jun-ichi Kashiwakura
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Noboru Suzuki,
Noboru Suzuki
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Hiroko Nagafuchi,
Hiroko Nagafuchi
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Mitsuhiro Takeno,
Mitsuhiro Takeno
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Yuko Takeba,
Yuko Takeba
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Yoshihiro Shimoyama,
Yoshihiro Shimoyama
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Tsuyoshi Sakane
Tsuyoshi Sakane
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
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Jun-ichi Kashiwakura
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Noboru Suzuki
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Hiroko Nagafuchi
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Mitsuhiro Takeno
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Yuko Takeba
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Yoshihiro Shimoyama
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Tsuyoshi Sakane
aDepartment of Immunology and the Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
1used in this paper: CAT, chloramphenicol acetyl transferase; ODN, oligodeoxynucleotide; p, plasmid; RSV, Rous sarcoma virus; RT, reverse transcription; SH, src homology
Received:
May 05 1999
Revision Requested:
July 19 1999
Accepted:
July 20 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (8): 1147–1154.
Article history
Received:
May 05 1999
Revision Requested:
July 19 1999
Accepted:
July 20 1999
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Jun-ichi Kashiwakura, Noboru Suzuki, Hiroko Nagafuchi, Mitsuhiro Takeno, Yuko Takeba, Yoshihiro Shimoyama, Tsuyoshi Sakane; 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. J Exp Med 18 October 1999; 190 (8): 1147–1154. doi: https://doi.org/10.1084/jem.190.8.1147
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