CTLA‐4 blockade inhibits induction of Helicobacter pylori‐associated gastritis in mice
The balance between Th1 and Th2 response determines the outcome of Helicobacter pylori infection. Interferon (IFN)‐γ plays an inductive role in gastric inflammation, whereas interleukin (IL)‐4 counterbalances Th1 response and suppresses the development of gastritis. Th cell response is regulated by co‐stimulatory factors. A co‐stimulatory molecule, cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4), plays an inhibitory role in IL‐2‐dependent cell growth and mediates an optimal inhibitory signal to Th1 and Th2 cells. We administered anti‐CTLA‐4 monoclonal antibody (MoAb), which blocks CTLA‐4 signalling, to examine the relative role for this signalling during maturation of Th1 and Th2 cells in H. pylori infection in mice. Mice treated by anti‐CTLA‐4 MoAb within the first week of infection showed an inhibition of gastric inflammation, accompanied by an increasing ratio of H. pylori‐specific IgG1/IgG2a  in  serum  following  infection.  Furthermore,  the  treatment  resulted  in  the higher ratio of IL‐4/IFN‐γ by splenocytes in response to H. pylori antigen at 6 weeks after infection, compared with untreated mice. These results suggest that the predominance of Th2 response by CTLA‐4 blockade leads to an inhibition of the development of gastric inflammation. CTLA‐4 signalling could contribute to the regulation of Th subsets and the development of gastric inflammation in H. pylori infection.