title: CD4+ CD25+ regulatory T cells modulate the T-cell and antibody responses in helicobacter-infected BALB/c mice.
abstract: Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.
authors.affiliation: Department of Microbiology and Immunology and the NHMRC Bacterial Pathogenesis Group, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Kaparakis
authors.forename: Karen L
authors.initials: KL
authors.lastname: Laurie
authors.forename: Odilia
authors.initials: O
authors.lastname: Wijburg
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.forename: Martin
authors.initials: M
authors.lastname: Pearse
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D015551:Autoimmunity; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000209:etiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007132:Immunoglobulin Isotypes / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D000907:Antibodies, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D007132:Immunoglobulin Isotypes