Role of Gastric Epithelial Cell-Derived Transforming Growth Factor in Reduced CD4 T Cell Proliferation and Development of Regulatory T Cells during Helicobacter pylori Infection

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 (TGF) plays a major role in these responses. GECs produced TGF1 and TGF2 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. Naïve CD4 T cell development into Tregs was also enhanced in the presence of GEC-derived TGF. Herein, we demonstrate a role for GEC-produced TGFin the inhibition of CD4 T cell responses seen during H. pylori infection.