Involvement of Helicaobacter pylori and hepatitis C virus in the crosstalk toward hepato-gastro carcinogenesis.

Th 1和Th 2细胞在感染过程中的免疫调节中起着重要作用。我们发现，幽门螺杆菌诱导Th 1细胞因子反应早期（2周），但主要是Th 2反应后（6周）在感染。这种转换主要由尿素酶特异性CD 4 ^+T细胞介导，与感染后期尿素酶特异性高亲和力JNK^+ Th 1细胞的丧失和低亲和力JNK^-（可能是Th 2）细胞的增加相关，同时幽门螺杆菌在6周时的定植水平比2周时高100倍，可能耐受高亲和力Th 1细胞。此外，在用表达gp 160的牛痘免疫的6周幽门螺杆菌感染小鼠中，HIV gp 160特异性CD 4 ^+ Th和CD 8 ^+ CTL分化为效应细胞受到损害，并且几乎检测不到牛痘感染刺激的血清IL-12。将脲酶特异性Th 2细胞连续转移至仅用表达gp 160的牛痘感染的小鼠，消除了gp 120应答的Th 1极化，下调了病毒特异性CTL应答，并延迟了病毒清除。因此，幽门螺杆菌尿素酶介导的从JNK^+ Th 1向JNK^-Th 2表型转变的免疫调节，以及之前的低IL-12应答可能是抗病毒免疫受损的关键步骤。另一方面，丙型肝炎病毒（HCV）是众所周知的肝肿瘤的病原体。HCV核心基因在人宿主细胞中的表达在转染后24小时激活了NFκB，NF κ B是炎性细胞因子和粘附素的转录上调元件，导致考克斯-2和前列腺素E2蛋白的高产量。提示HCV核心蛋白表达引起宿主细胞内炎性细胞因子和粘附素的表达，加速了肝-胃癌的发生。

Th1 and Th2 cells play a central role in immunoregulation during infection. We show that H.pylori induces Th1 cytokine responses early (2wk) but predominantly Th2 responses later (6wk) in infection. The switch is principally mediated by urease-specific CD4^+T cells, and correlates with a loss of urease-specific high avidity JNK^+ Th1 and gain of low avidity JNK^- (possibly Th2) cells at the later stage of infection, concomitant with a 100-fold higher colonization level of H.pylori at 6 wk than at 2wk that might tolerize high avidity Th1 cells. Furthermore, differentiation of HIV gp160-specific CD4^+ Th and CD8^+ CTL into effector cells is impaired in 6-wk H.pylori-infected mice immunized with vaccinia expressing gp160, and serum IL-12 stimulated by vaccinia infection is barely detectable. Adoptive transfer of urease-specific Th2 cells to mice infected only with gp160-expressing vaccinia abrogates Th1 polarization of the gp120 response, downmodulates virus-specific CTL responses, and delays virus clearance. Therefore, the H.pylori urease-mediated immunoregulation in the switch from JNK^+ Th1 to JNK^-Th2 phenotype, and the preceding low IL-12 response are likely critical steps in the impairment of antiviral immunity. On the other hand, hepatitis C virus (HCV) is well known as a causative agent of hepatome. HCV core gene expression in the human host cells activated NFκB, a transcriptional upregulatory element for inflammatory cytokines and adhesins at 24hr post transfection, resulting in high production of COX-2 and prostaglandin E2 proteins. That suggest that HCV core expression causing inflammatory cytokines and adhesins in the host cells accerates hapato-gastro carcinogenesis.