Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.
Helicobacter bacteria colonize in the stomach and induce strong, specific local and systemic humoral and cell-mediated immunity. Helicobacter binds to the host epithelial cells, directly triggering the recruitment of neutrophils. Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4(+) T cells. The mechanisms underlying the development of T(h)1 cell-mediated chronic gastritis, however, are not clear. Peyer's patches (PPs), the major inductive sites for mucosal immunity in the gut system, might orchestrate Helicobacter-specific local and systemic humoral and cell-mediated immunity. To examine the roles of PPs in the development of Helicobacter-induced gastritis, we generated PP-null mice that normally develop well-organized lymphoid organs except for PPs and intra-gastrically infected the resulting PP-null mice with Helicobacter felis. PP deficiency severely impaired both the development of T(h)1 cell-mediated gastritis induced by Helicobacter and the production of anti-Helicobacter antibodies despite marked bacterial colonization of the gastric mucosa. Although PP deficiency did not impair the differentiation of Helicobacter-specific CD4(+) T cells into IFN-gamma--producing T(h)1 cells, Helicobacter-specific IFN-gamma--producing CD4(+) T cells in PP-null mice lacked the ability to migrate into Helicobacter-colonized gastric mucosa. These findings suggest that PPs have an important role in Helicobacter-specific local and systemic humoral and cell-mediated immunity, including the development of Helicobacter-induced gastritis.
Kiriya
Keiichi
K
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Watanabe
Norihiko
N
Nishio
Akiyoshi
A
Okazaki
Kazuichi
K
Kido
Masahiro
M
Saga
Kazuyuki
K
Tanaka
Junya
J
Akamatsu
Takuji
T
Ohashi
Shinya
S
Asada
Masanori
M
Fukui
Toshiro
T
Chiba
Tsutomu
T
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019742:Chemokines, CC / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D044922:Helicobacter felis / Q000254:growth & development; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C499308:Rag2 protein, mouse; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D007371:Interferon-gamma