Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model
Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model
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DOI：
10.1111/j.1365-2222.2004.01981.x
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发表时间：
2004-06-01
影响因子：
6.1
通讯作者：
Suzuki, N
中科院分区：
文献类型：
--
作者：
Takeno, M;Yoshikawa, H;Suzuki, N
Th 1和Th 2细胞分别由IL-12和IL-4存在下的抗原刺激产生，涉及包括过敏性和自身免疫性疾病在内的各种疾病的病理学。Txk/Rlk是Tec家族酪氨酸激酶的成员。目的探讨Txk表达质粒在小鼠体内是否引起Th 1/Th 2漂移，从而降低循环IgE水平。免疫印迹和免疫细胞化学染色检测脾细胞中Txk的表达。结果用含HVJ载体的txk表达质粒诱导脾细胞表达Txk，用ELISA法检测血清IG浓度。脾细胞表现出增强的Th 1特异性细胞因子的产生;与对照质粒给药小鼠相比，TXK给药小鼠的脾细胞以抗原特异性方式产生更多的IFN-γ。两组小鼠脾细胞的IL-2和IL-4分泌量相当。Txk给药不降低血清IgG浓度。显著降低血清总IgE水平和反映Th 1/Th 2平衡的IgG 1/IgG 2a比值。此外，TXK管理减少卵清蛋白（OVA）致敏mice.Conclusion血清中特异性IgE水平，因此，TXK增强IFN-γ分泌，从而调节Th 1/Th 2细胞因子平衡，导致血清IgE降低。
Background Th1 and Th2 cells, resulting from antigenic stimulation in the presence of IL-12 and IL-4, respectively, are implicated in the pathology of various diseases including allergic and autoimmune diseases. Txk/Rlk is a member of Tec family tyrosine kinases. We reported that Txk acts as a Th1-specific transcription factor in the T lymphocytes.Objective In this study we have asked whether administration of txk expression plasmid brings about a Th1/Th2 shift in vivo of the mice, and subsequent reduction of circulating IgE.Methods Mice were administered a txk expression plasmid with hemagglutinating virus of Japan (HVJ) envelope vector. Txk expressions in spleen cells were assessed by immunoblotting and immunocytochemical staining. Cytokine productions by the spleen cells and serum Ig concentrations were studied by ELISA.Results Administration of a txk expression plasmid with HVJ vector induced expression of Txk in the spleen cells. The spleen cells showed enhanced Th1-specific cytokine production; spleen cells from the txk administered mice produced more IFN-gamma as compared with those from control plasmid-administered mice in an antigen-specific manner. IL-2 and IL-4 secretions of the spleen cells were comparable between the two mouse groups. Txk administration did not reduce serum IgG concentration. It markedly reduced total IgE level and an IgG1/IgG2a ratio, reflection of Th1/Th2 balance, in sera. Furthermore, txk administration reduced ovalbumin (OVA)-specific IgE levels in sera of the OVA sensitized mice.Conclusion Thus, Txk enhances IFN-gamma secretion and thus modulates Th1/Th2 cytokine balance, leading to reduction of serum IgE.