Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against helicobacter infection in mice.
OBJECTIVE
The integrin alpha(4)beta(7) mediates homing of effector/memory lymphocytes to the intestine and the mucosa-associated lymphoid tissue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T lymphocytes to home to the stomach and their role in immunization-mediated protection against Helicobacter felis infection.


METHODS
Gastric lamina propria and circulating mononucleated cells of naive, infected, and immunized Swiss Webster mice were isolated, and alpha(4)beta(7)-integrin expression was quantified by flow cytometry on CD4(+) T lymphocytes. Anti-alpha(4)beta(7)-integrin antibody was used to block alpha(4)beta(7) function in vivo.


RESULTS
In naive mice, alpha(4)beta(7)(hi) CD4(+) T cells were enriched approximately 10-fold in the gastric mucosa compared with peripheral blood (P<0.0001). Chronic H. felis infection did not alter these proportions, but oral immunization with H. felis sonicate plus cholera toxin (CT) or with CT alone markedly increased gastric alpha(4)beta(7)(hi) CD4(+) T cells compared with naive and infected controls (P = 0.0008 and P = 0.002 for H. felis sonicate and CT, respectively). Anti-alpha(4)beta(7)-integrin antibody blocked the protection induced by oral immunization with H. felis sonicate and CT.


CONCLUSIONS
The integrin alpha(4)beta(7) participates in the homing of CD4(+) T lymphocytes to the stomach and in the protection of the gastric mucosa against H. felis infection.
Michetti
M
M
Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. pmichett@caregroup.harvard.edu
Kelly
C P
CP
Kraehenbuhl
J P
JP
Bouzourene
H
H
Michetti
P
P
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D016998:Helicobacter / Q000276:immunology; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007107:Immune System / Q000502:physiology*; D007114:Immunization; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D016201:Receptors, Lymphocyte Homing / Q000502:physiology
D016023:Integrins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7