gammadelta T cells increase with gastric mucosal interleukin (IL)-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.
OBJECTIVE
The purpose of this study was to investigate possible factors that could impact on gammadelta T cell accumulation in the gastric mucosa.


METHODS
Subjects were 22 Helicobacter pylori (H. pylori)-free and 75 H. pylori-infected mucosa biopsies classified into grades I approximately III gastritis as per our previous study. The number of gammadelta- and 45 RO-positive T cells were determined by immunostaining. Gastric mucosal anti-H. pylori urease specific antibodies and interleukin (IL)-1beta, IL-2, 4, 7, 10 and IL-12 levels were assayed by enzyme-linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in gammadelta T cells stimulated by H. pylori urease were also evaluated.


RESULTS
The gammadelta T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. gammadelta T cell count was significantly correlated with IL-1beta and interleukin-7 (IL-7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many gammadelta T cells. After H. pylori eradication therapy, the gammadelta T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL-7 stimulation in both peripheral and mucosal gammadelta T cells. Interferon (IFN)-gamma and IL-10 production was also stimulated by H. pylori urease in peripheral gammadelta T cells.


CONCLUSIONS
Gastric mucosal increases in IL-7 and IL-1beta closely corresponded to the accumulation of gammadelta T cells in gastric mucosa. An association was also seen between gammadelta T cell accumulation and H. pylori urease-specific Ig levels.
Futagami
Seiji
S
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. Seiji-f@nms.ac.jp
Hiratsuka
Tetsuro
T
Suzuki
Kenji
K
Kusunoki
Masanori
M
Wada
Ken
K
Miyake
Kazumasa
K
Ohashi
Kazushi
K
Shimizu
Masumi
M
Takahashi
Hidemi
H
Gudis
Katya
K
Kato
Shunji
S
Tsukui
Taku
T
Sakamoto
Choitsu
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology; D014510:Urease / Q000276:immunology*
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; C515334:CCR2 protein, human; C508605:IL7 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens; D014510:Urease