T细胞疫苗对实验性自身免疫性肝炎的影响

Effect of T-cell vaccination in murine experimental autoimmune hepatitis

目的 观察T细胞疫苗对实验性自身免疫性肝炎(EAH)的影响。 方法 在第1天和第7天分别以新鲜制备的含蛋白质浓度为0.5～2.0 g/L的S-100肝抗原0.5 ml与等体积的弗氏完全佐剂充分乳化后予小鼠腹腔注射,以诱导EAH的产生。T细胞疫苗采用EAH模型小鼠首次免疫后2周的脾脏细胞灭活而成。模型组(6只),在首次免疫前第14天和免疫第7天,每只小鼠腹腔注射磷酸盐缓冲液1 ml;T细胞疫苗组(8只)和无关T细胞疫苗组(6只)在首次免疫前第14天和免疫第7天分别腹腔注射T细胞疫苗和无关T细胞疫苗悬液各1 ml。 结果 T细胞疫苗预防组的肝组织病变严重程度和血清丙氨酸氨基转移酶水平较模型组显著减低,分别为1.44±0.88对2.3 3±0.87,t=2.24,P<0.05和63.0±23.4对115.1±39.6,t=2.37,P<0.01;而无关T细胞疫苗组无显著变化。 结论 T细胞疫苗在小鼠EAH中能有效缓解肝内炎症坏死病变。以无关T细胞用作T细胞疫苗时无效,提示T细胞疫苗具有独特型特异性。

Objective To investigate the effect of T-cell vaccination in murine experimental autoimmune hepatitis (EAH), Methods To induce the EAH model, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally to C57B1/6 at day 1 and day 7. For T-cell vaccination, splenocytes were removed from animal 2 weeks after induction of EAH and from control animals, and activated in vitro by mitogen stimulation with Concanavalin A (Con A ), then inactivated by mitomycin and injected at 5 × 107 cells per animal as T-cell vaccination at 14 before first induction of EAH and 7 days on the second induction of EAH. Result The histological grade and serum ALT level of the mice who received T-cell vaccination were decrease significantly, compared with that of model group (1.44 ± 0.88 vs, 2.33 ± 0.87,t=2.24, P<0.05; 63.0 U/L ± 23.4 U/L vs 115. U/L1 ± 39.6 U/L, t=2.37, P<0.01, respectively); there was no significant change in mice who received irrelevant T-cell vaccination. Conclusion T-cell vaccination with T cells from EAH animals, but not with irrelevant T cells, was able to protect animals from EAH.