Analysis of Txk functions in the development of Th1 cells and its application for treatment of autoimmune and allergic diseases

辅助型T细胞1(Th1)和辅助性T细胞2(Th2)分别在白介素12(IL-12)和白介素4(IL-4)的存在下产生，参与包括变态反应性疾病和自身免疫性疾病在内的多种疾病的病理过程。我们已经报道了TXK在T淋巴细胞中作为Th1细胞特异性转录因子。我们发现IL-12、IL-18和干扰素-g对小鼠脾细胞TXK的表达有正向影响，而IL-4和IL-13对TXK的表达有负影响。与以抗原特异性方式注射对照质粒的小鼠相比，注射TXK表达质粒的小鼠脾细胞产生更多的干扰素-γ。两组小鼠脾细胞分泌IL-2和IL-4的能力相当。通心康不降低血清免疫球蛋白水平，但能显著降低血清总IgE水平和反映Th1/Th2平衡的IgG1/IfG2a比值。此外，TXK还能降低小鼠血清中用于免疫的抗原特异性IgE水平。因此，TXK促进干扰素-g的分泌，从而调节Th1/Th2细胞因子平衡，导致体内抗原特异性的血清IgE降低。

T helper type 1 (Th1) and Th2 cells, resulting from antigenic stimulation in the presence of interleukin (IL)-12 and IL-4, respectively, are implicated in the pathology of diseases including allergic and autoimmune diseases.Txk/Rlk is a member of Tec family tyrosine kinases. We have reported that Txk acts as a Th1 cell specific transcription factor in the T lymphocytes. We found that Txk expression was affected positively by IL-12, IL-18 and IFN-g and negatively by IL-4 and IL-13.We next studied whether administration of txk expression plasmid induced expression of Txk in their spleen cells. The spleen cells from the mice administered txk expression plasmid produced more IFN-gamma as compared with those from mice administered control plasmid in an antigen specific manner. IL-2 and IL-4 secretion of the spleen cells were comparable between the two mouse groups. Txk administration did not reduce serum IgG concentration.However, it markedly reduced serum total IgE level and an IgG1/IfG2a ration, reflection of Th1/Th2 balance. Furthermore, txk administration reduced the antigen specific IgE levels in sera of the mice, which was used for immunizing mice. Thus, Txk enhances IFN-g secretion and thus modulates Th1/Th2 cytokine balance, leading to reduction of serum IgE in an antigen specific manner in vivo.