Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against Helicobacter infection in mice

Background & Aims: The integrin alpha(4)beta(7) mediates homing of effector /memory lymphocytes to the intestine and the mucosa-associated lymphoid tis sue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T lympho cytes to home to the stomach and their role in immunization-mediated protec tion 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 q uantified by flow cytometry on CD4(+) T lymphocytes, Anti-alpha(4)beta(7)-i ntegrin antibody was used to block alpha(4)beta(7) function in vivo. Result s: In naive mice, alpha(4)beta(7)(hi) CD4(+) T cells were enriched approxim ately 10-fold in the gastric mucosa compared with peripheral blood (P < 0,0 001), Chronic H. felis infection did not alter these proportions, but oral immunization with H. felis sonicate plus cholera toxin (CT) or with CT alon e markedly increased gastric alpha(4)beta(7)(hi) CD4(+) T cells compared wi th naive and infected controls (P = 0.0008 and P = 0.002 for H. felis sonic ate and CT, respectively). Anti-alpha(4)beta(7)-integrin antibody blocked t he protection induced by oral immunization with H. felis sonicate and CT. C onclusions: 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.