title: CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo.
abstract: OBJECTIVE
  Helicobacter pylori infects more than half of the world's population. In contrast to most other pathogens, the microbe persists for the virtual life of its host. It is unclear why the immune system is unable to eliminate the infection, but recent studies suggested that CD4+/CD25+/Foxp3+ regulatory T cells may be involved in this process.
  
  
  METHODS
  By using a mouse model of infection and gastric biopsies from 108 patients, we performed a detailed descriptive and functional characterization of the Helicobacter-induced CD25+/Foxp3+ T-cell response.
  
  
  RESULTS
  In C57BL/6 mice, H pylori induced a marked gastric Foxp3+ T-cell response, which increased over several months together with the severity of inflammation, until a stable homeostatic situation became established. Accordingly, in Helicobacter-infected patients, but not in uninfected individuals, large numbers of gastric Foxp3+ T cells were detected immunohistochemically. To define the functional in vivo relevance of this response, CD25+ cells were depleted systemically in mice by using an anti-CD25 monoclonal antibody (PC61). Already 4 weeks after infection, PC61-treated mice, but not untreated animals, developed a severe gastritis with heightened cytokine expression and increased numbers of mucosal T cells, B cells, and macrophages. This was accompanied by increased titers of H pylori-specific IgG1 and IgG2c antibodies in the sera of PC61-treated mice. This increased gastric inflammatory response in CD25-depleted mice was associated with reduced bacterial loads.
  
  
  CONCLUSIONS
  CD25+/Foxp3+ T cells actively participate in the immune response to H pylori. In vivo depletion of these cells in infected mice leads to increased gastric inflammation and reduced bacterial colonization.
authors.affiliation: Second Department of Internal Medicine and Gastroenterology, Technical University of Munich, Munich, Germany. Roland.Rad@lrz.tum.de
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Lena
authors.initials: L
authors.lastname: Brenner
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwendy
authors.forename: Laura
authors.initials: L
authors.lastname: Layland
authors.forename: Clarissa Prazeres
authors.initials: CP
authors.lastname: da Costa
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reindl
authors.forename: Anar
authors.initials: A
authors.lastname: Dossumbekova
authors.forename: Mathias
authors.initials: M
authors.lastname: Friedrich
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001706:Biopsy; D002908:Chronic Disease; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D007150:Immunohistochemistry; D008212:Lymphocyte Depletion; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial; D004269:DNA, Bacterial; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2