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)-gamma 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-gamma 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.
Watanabe
K
K
Department of Infectious Diseases and General Medicine, Oita University, Oita, Japan. kwata@oita-med.ac.jp
Murakami
K
K
Sato
R
R
Okimoto
T
T
Maeda
K
K
Nasu
M
M
Nishizono
A
A
Fujioka
T
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D060908:CTLA-4 Antigen; D005260:Female; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma