title: Cross-primed CD8+ cytotoxic T cells induce severe Helicobacter-associated gastritis in the absence of CD4+ T cells.
abstract: BACKGROUND
  Although previous studies have reported important roles of CD4(+) type 1-helper T cells and regulatory T cells in Helicobacter-associated gastritis, the significance of CD8(+) cytotoxic T cells remains unknown. To study the roles of CD8(+) T cells, we examined the immune response in the gastric mucosa of Helicobacter felis-infected major histocompatibility complex (MHC) class II-deficient (II(-/-)) mice, which lack CD4(+) T cells.
  
  
  METHODS
  Stomachs from H. felis-infected wild-type and infected MHC II(-/-) mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti-H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated.
  
  
  RESULTS
  H. felis-infected MHC II(-/-) mice developed severe gastritis, accompanied by marked infiltration of CD8(+) cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II(-/-) mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4(+) cells, and no Foxp3-positive cells were detected in the gastric mucosa of the infected MHC II(-/-) mice. The expression of the interleukin-1beta and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II(-/-) mice. Serum levels of anti-H. felis antibodies were lower in the infected MHC II(-/-) mice, despite severe gastritis.
  
  
  CONCLUSIONS
  The present study suggests that cross-primed CD8(+) cytotoxic T cells can induce severe H.-associated gastritis in the absence of CD4(+) helper T cells and that Foxp3-positive cells may have an important role in the control of gastric inflammation.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kasahara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Saga
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Uza
authors.forename: Satoru
authors.initials: S
authors.lastname: Ueno
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kido
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D044922:Helicobacter felis / Q000276:immunology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse