Impaired development of HIV-1 gp160-specific CD8(+) cytotoxic T cells by adelayed switch from Th1 to Th2 cytokine phenotype in mice with Helicobacter pylori infection

Th1 and Th2 cells play a central role in immunoregulation during infection. We show that Helicobacter pylori induces Th1 cytokine responses early (2 w eeks) but predominantly Th2 responses later (6 weeks) in infection. The swi tch is principally mediated by urease-specific CD4(+) T cells, and correlat es with a loss of urease-specific high-avidity JNK(+) Th1 and gain of low-a vidity JNK(-) (possibly Th2) cells at the later stage of infection, concomi tant with a 100-fold higher colonization level of H. pylori at 6 weeks than at 2 weeks that might tolerize high-avidity Th1 cells. Furthermore, differ entiation of HIV gp160-specific CD4(+) Th and CD8(+) cytotoxic T lymphocyte s (CTL) into effector cells is impaired in g-week H. pylori-infected mice i mmunized with vaccinia expressing gp160, and serum IL-12 stimulated by vacc inia infection is barely detectable. Adoptive transfer of urease-specific T h2 cells to mice infected only with gp160-expressing vaccinia abrogates Th1 polarization of the gp120 response, downmodulates virus-specific CTL respo nses, and delays virus clearance. Therefore, the H. pylori urease-mediated immunoregulation in the switch from JNK(+) Th1 to JNK- Th2 phenotype, and t he preceding low IL-12 response, are likely critical steps in the impairmen t of antiviral immunity.