Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection

Abstract

Helicobacter pylori infection is associated with gastritis, ulcers, and gastric cancer. The infection becomes chronic as the host response is unable to clear it. Gastric epithelial cells (GEC) play an important role during the host response, and their expression of class II MHC and costimulatory molecules such as CD80 and CD86 suggests their role in local Ag presentation. Although T cells are recruited to the infected gastric mucosa, they have been reported to be hyporesponsive. In this study, we detected the expression of B7-H1 (programmed death-1 ligand 1), a member of B7 family of proteins associated with T cell inhibition on GEC. Quantitative real-time RT-PCR revealed that B7-H1 expression increased significantly on GEC after H. pylori infection. Western blot analysis showed that B7-H1 expression was induced by various H. pylori strains and was independent of H. pylori virulence factors such as Cag, VacA, and Urease. The functional role of B7-H1 in the cross talk between GEC and T cells was assessed by coculturing GEC or H. pylori-infected GEC with CD4+ T cells isolated from peripheral blood. Using blocking Abs to B7-H1 revealed that B7-H1 was involved in the suppression of T cell proliferation and IL-2 synthesis, and thus suggested a role for B7-H1 on the epithelium as a contributor in the chronicity of H. pylori infection.

Expression of the Programmed Death Ligand 1, B7-H1, on Gastric Epithelial Cells afterHelicobacter pyloriExposure Promotes Development of CD4+CD25+FoxP3+Regulatory T Cells

“…Similarly, in infected mice, depleting the Treg cells led to increased pathology (20,21). Since Treg cells may play an important role in the impaired T-cell responses during H. pylori infection, and we and others have shown that B7-H1 also plays a role in T-cell suppression or generation of Treg cells (5,12,30), we sought to determine the role of B7-H1 on GEC in the development of CD4 ϩ CD25 high FoxP3 ϩ Treg cells during H. pylori infection. In this study, we show that coculture of naïve CD4 ϩ T cells with H. pylori-exposed GEC generates CD4 ϩ CD25 high FoxP3 ϩ T cells.…”

“…Since binding of B7-H1 to the programmed death 1 receptor on T cells causes them to undergo anergy or apoptosis (23,27), B7-H1 may play a key role in the chronicity of those infections and associated inflammatory responses. H. pylori-exposed GEC incubated with isolated CD4 ϩ T cells resulted in decreased proliferation and IL-2 production, but this inhibition was abrogated by anti-B7-H1 blocking antibodies (5). These findings suggest that B7-H1 plays an important role in T-cell inhibition during H. pylori infection.…”

“…Although gastric epithelial cells (GEC) have been shown to express the class II major histcompatibility complex and to function as antigen-presenting cells (3,10), we have recently shown that the coinhibitory molecule, the programmed death ligand 1, or B7-H1, is up-regulated on GEC during exposure to H. pylori both in vitro and in vivo (5). Since binding of B7-H1 to the programmed death 1 receptor on T cells causes them to undergo anergy or apoptosis (23,27), B7-H1 may play a key role in the chronicity of those infections and associated inflammatory responses.…”

Programmed Death (PD)-1:PD-Ligand 1/PD-Ligand 2 Pathway Inhibits T Cell Effector Functions during Human Tuberculosis

“…Hence, it was shown that the PD-1:PD-Ls pathway contributes directly to T cell dysfunction and lack of viral control in established chronic infection both in mice (35) and humans (36 -38). Similarly, persisting infection with pathogens other than viruses, like Helicobacter pylori and Porphyromonas gingivalis, showed elevated expression of PD-L1 on gastric epithelial cells (39) and monocytes (40), respectively, suggesting a potential involvement of PD-L1 in promoting chronic infection (39). However, the function of the PD-1:PD-Ls interactions during the regulatory pathways that contribute to persistence of intracellular bacteria has not been investigated.…”

“…Besides, during hepatitis B virus infection, PD-1:PD-L1 interactions were shown to contribute to the suppression of IFN-␥ secretion following Ag recognition in the liver (59). Furthermore, in infection with H. pylori, anti-PD-L1 was shown to increased T cell proliferation and IL-12 secretion (39). Accordingly, in this work we demonstrated that the PD-1:PD-Ls pathway displayed a coinhibitory role on IFN-␥ production during chronic M. tuberculosis infection.…”