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

我们将丙酸杆菌诱导的新生儿去胸腺小鼠（NTx）或正常小鼠的脾细胞移植到肝脏。并对NTx小鼠和正常小鼠进行检测。只有当供体和受体都是NTx小鼠时，58%的受体小鼠才会出现肝炎。供体和受体均为正常小鼠时，未见肝炎。为转移肝炎，供鼠和受鼠均需进行新生儿胸腺切除术。NTx小鼠表现出抑制功能下降和胸腺外自身反应性T细胞增加，这在自身反应性克隆的增殖和肝炎的延长中起重要作用。流式细胞术分析发现，pacnes和LSP诱导的NTx小鼠肝脏中CD4+、Vbeta4+ T细胞增加。提示pacnes和LPS诱导NTx小鼠肝炎可能是通过细胞介导机制发生的，作用细胞为CD4+、Vbeta4+ T细胞。注射痤疮p.a nes和LPS使NTx肝炎小鼠的Vbeta4+ T细胞缺失的脾脏细胞转移，未观察到肝炎的转移。Vbeta4+ T细胞是肝炎转移所必需的。我们认为pacnes和LPS诱导NTx小鼠的实验性肝炎涉及自身免疫机制，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.