Alteration of intestinal intraepithelial lymphocytes and increased bacterial translocation in a murine model of cirrhosis.
Alterations in immunological defense in the gut may lead to the bacterial infection that is frequently associated with cirrhosis of the liver. The aim of this study was to investigate the changes in distribution and function of intestinal intraepithelial lymphocytes (IELs) in relation to intestinal barrier dysfunction in experimental cirrhosis. Cirrhosis was induced in mice by treatment with carbon tetrachloride (CCl4) intraperitoneally with 5% alcohol in drinking water for 12 weeks. Bacterial translocation was assessed in mesenteric lymph nodes (MLNs) by the transport of fluorescence-labeled latex beads and by bacteriological cultures. The lymphocyte subpopulation was compared in three groups (cirrhosis, alcohol alone and controls). IFN-gamma production from isolated IELs was determined by ELISA after stimulation with anti-CD3 or IL-12/IL-18. The total number of IELs significantly increased in the cirrhosis and alcohol groups. There was a preferential increase in TCRgammadelta+CD8+ population in the alcohol group, but no change in cirrhosis. Bacterial translocation was negative in the control group, and a small number was noted in the alcohol group, whereas it was significantly noted in the cirrhosis group. Although the number of IEL was significantly increased in the cirrhosis group, their proliferative response was decreased, and IFN-gamma production from each IEL was markedly diminished in either stimulation by anti-CD3 or IL-12/IL-18. These changes were more remarkable in the cirrhosis group than in the alcohol group. In conclusion, bacterial translocation due to intestinal barrier dysfunction in cirrhosis may be closely correlated with the alteration of the immune function in IELs.
Inamura
Toshiaki
T
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Miura
Soichiro
S
Tsuzuki
Yoshikazu
Y
Hara
Yuriko
Y
Hokari
Ryota
R
Ogawa
Toshiko
T
Teramoto
Ken
K
Watanabe
Chikako
C
Kobayashi
Hisashi
H
Nagata
Hiroshi
H
Ishii
Hiromasa
H
D000818:Animals; D018988:Bacterial Translocation; D017252:CD3 Complex / Q000494:pharmacology; D002251:Carbon Tetrachloride; D000431:Ethanol; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007422:Intestines / Q000276:immunology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
D017252:CD3 Complex; D020382:Interleukin-18; D018664:Interleukin-12; D000431:Ethanol; D002251:Carbon Tetrachloride