Development of Specific Immunotherapy For Autoimmune Hepatitis-Resaerch On T cell Vaccination

我们从新生胸腺切除(NTX)小鼠或丙酸杆菌诱导的肝炎正常小鼠身上转移了脾细胞。对NTX小鼠和正常小鼠的痤疮(P.acnes，P.acnes)和脂多糖(LPS)进行检测。仅当供体和受体均为NTX小鼠时，才有58%的受体小鼠出现肝炎。当供体或受体为正常小鼠时，未观察到肝炎。新生胸腺切除对供体和受体小鼠的肝炎转移是必要的。NTX小鼠抑制功能降低，胸腺外自身反应性T细胞增多，在自身反应性克隆的增殖和肝炎的延长中起重要作用。流式细胞仪分析显示，痤疮肺炎支原体和脂多糖诱导的NTX小鼠肝炎模型肝脏中的CD4+、Vbeta4+T细胞明显增多，提示痤疮支原体和脂多糖诱导的NTX小鼠肝炎的发生可能是细胞介导的机制，效应细胞为CD4+、Vbeta4+T细胞。注射痤疮杆菌和脂多糖的NTX肝炎小鼠的Vbeta4+T细胞耗竭的脾细胞被转移，但未观察到肝炎转移。Vbeta4+T细胞是肝炎病毒转移所必需的。提示痤疮螺旋体和脂多糖诱导的NTX小鼠实验性肝炎与自身免疫机制有关，效应细胞为CD4+、Vbeta4+T细胞。

We transferred spleen cells from neonatally thymectomized (NTx) mice or normal mice with hepatitis induced by administration of Propionibacterium. acnes (P.acnes) and LPS to NTx mice or normal mice and examined. Hepatitis were observed in 58% recipient mice only when both donor and recipient were NTx mice. When donor or recipient was normal mice, hepatitis was not observed. Neonatal thymectomy was necessory in donor and recipient mice for transfer of hepatitis. NTx mice showed decreased suppressor function and increased extrathymic autoreactive T cells which play an important role in the multiplication of autoreactive clones as well as the prolongation of hepatitis. By flow cytometric analysis, CD4+, Vbeta4+ T cells were increased in the liver of NTx mice with hepatitis induced by P.acnes and LSP.These findings suggest that hepatitis induced in NTx mice by P.acnes and LPS may occur due to the cell-mediated mechanism and the effector cells were CD4+, Vbeta4+ T cells. When Vbeta4+ T cell-depleted spleen cells of NTx mice with hepatitis by injection of P.acnes and LPS were transferred, transfer of hepatitis was not observed. Vbeta4+ T cell is necessory for transfer of hepatitis. We suggest that experimental hepatitis induced in NTx mice by P.acnes and LPS involved autoimmune mechanism and the effector cells were CD4+, Vbeta4+ T.cells.