Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon Production in Human T Lymphocytes

Correspondence to: Tsuyoshi Sakane, Depts. of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. Tel:81-44-977-8111 ext. 4014 Fax:81-44-975-4347 E-mail:t2sakane{at}marianna-u.ac.jp.

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- producing potential. Txk transfection of Jurkat T cells resulted in a several-fold increase of IFN- mRNA expression and protein production; interleukin (IL)-2 and IL-4 production were unaffected. Antisense oligodeoxynucleotide of Txk specifically inhibited IFN- 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- promoter/enhancer (pIFN-[-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- 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- production by the cells, indicating that nuclear localization of Txk is obligatory for the enhanced IFN- 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- production by the cells through Th1 cell–specific positive transcriptional regulation of the IFN- gene.

Key Words: Txk, gene transcription, T helper 1/T helper 2 cells, human, interferon

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