title: Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4+ T cell proliferation and development of regulatory T cells during Helicobacter pylori infection.
abstract: Gastric epithelial cells (GECs) express the class II major histocompatibility complex (MHC) and costimulatory molecules, enabling them to act as antigen-presenting cells (APCs) and affect local T cell responses. During Helicobacter pylori infection, GECs respond by releasing proinflammatory cytokines and by increasing the surface expression of immunologically relevant receptors, including class II MHC. The CD4(+) T cell response during H. pylori infection is skewed toward a Th1 response, but these cells remain hyporesponsive. Activated T cells show decreased proliferation during H. pylori infection, and CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) are present at the site of infection. In this study, we examined the mechanisms surrounding the CD4(+) T cell responses during H. pylori infection and found that transforming growth factor β (TGF-β) plays a major role in these responses. GECs produced TGF-β1 and TGF-β2 in response to infection. Activated CD4(+) T cells in culture with H. pylori-treated GECs were decreased in proliferation but increased upon neutralization of TGF-β. Naïve CD4(+) T cell development into Tregs was also enhanced in the presence of GEC-derived TGF-β. Herein, we demonstrate a role for GEC-produced TGF-β in the inhibition of CD4(+) T cell responses seen during H. pylori infection.
authors.affiliation: Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131,USA. ebeswick@salud.unm.edu
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Pinchuk
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Earley
authors.forename: David A
authors.initials: DA
authors.lastname: Schmitt
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reyes
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005802:Genes, MHC Class II; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta