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 CD4r+ 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.
All Science Journal Classification (ASJC) codes
- Infectious Diseases