Impaired development of HIV-1 gp160-specific CD8(+) cytotoxic T cells by a delayed 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 weeks) but predominantly Th2 responses later (6 weeks) 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 weeks than at 2 weeks that might tolerize high-avidity Th1 cells. Furthermore, differentiation of HIV gp160-specific CD4(+) Th and CD8(+) cytotoxic T lymphocytes (CTL) into effector cells is impaired in 6-week 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, down-modulates 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.
Shirai
M
M
Department of Microbiology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Fujinaga
R
R
Masaki
T
T
Berzofsky
J A
JA
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D016207:Cytokines; D019302:HIV Envelope Protein gp160; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases