| Research Abstract |
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.
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