细胞信号转导介导与日本血吸虫特异性Th1/Th2免疫偏移

分别于小鼠感染日本血吸虫后 0、 4、 6、 8和 12周 ,取脾淋巴细胞体外培养 ,进行细胞信号转导抑制试验 ,观察酪氨酸蛋白激酶 (TPK )、蛋白激酶C (PKC )和磷酯酰肌醇 3 激酶 (PI 3 K )特异性抑制剂 (Tyrphostin 2 5、D sphingosine和Wort mannin )分别特异性抑制和不同组合抑制TPK、PKC和PI 3K后 ,对小鼠脾淋巴细胞经虫卵可溶性抗原 (SEA )诱生IL 2、IFN γ和IL 4的表达水平及对Th1/Th2免疫偏移的影响。结果发现Tyrphostin 2 5对IL 2、IFN γ和IL 4水平的抑制作用均非常显著(P <0 0 1) ,D sphingosine主要影响IL 4的表达 (P <0 0 1) ,而Wortmannin则主要影响IFN γ的表达 (P <0 0 1) ,Tyrphostin 2 5和Wortmannin联合应用可完全阻断IL 2的表达及增强对IFN γ的抑制作用 ,Tyrphostin 2 5和D sphingosine联合应用可完全阻断IL 4的表达。对反映Th1/Th2免疫平衡的Th2分化指数分析表明 ,D sphingosine可使Th2免疫应答优势减弱 ,而Wort mannin则可使Th2免疫应答优势增强。研究结果表明 ,干预细胞信号转导可调节日本血吸虫特异性Th1/Th2细胞因子表达水平及Th1/Th2免疫偏移 ,为探索控制日本血吸虫卵肉芽肿病变的潜在新途径 ,提供了实验依据。

Effects of Inhibitors for Signaling on Specific Th1/Th2 Immune Deviation of Schis tosoma Japonicum

Murine spleen lymphocyte cultures were made at 0,4,6,8 and 12 weeks after infection of mice with Schistosoma japonicum,and the effects of inhibitors on the cell signal transduction were observed. Experimental results showed that Tyrphostin-25,a specific inhibitor to tyrosine protein kinase (TPK),could inhibit the expression of IL-2 IFN-γ and IL-4;D-sphingosine,a specific inhibitor to protein kinase C(PKC) mainly inhibited the expression of IL-4;and Wortmannin,the specific inhibitor to phosphatidylinositol-3-kinase (PI 3-K),mainly inhibited the expression of interferons gamme. The combined use of Tyrphostin-25 and Wortmannin could completely block the expression of IL-2,and enhance the inhibitory effect to interferons gamme. On the other hand,the combination of Tyrphostin-25 and D-sphingostine could entirely block the expression of IL-4. The results of analysis by the Th2 differentiation index that used to evaluate the immune balance of Th1/Th2 cells,showed that Th2 response was reduced by using D-sphingosine,but enhanced when Wortmannin was used. These findings suggest that inhibitors of the signal transduction can modulate Th1/Th2 immune deviation and this kind of study provide a novel potential approach for controlling the egg granuloma formation of Schistosoma japonicum.