Periportal and sinusoidal liver dendritic cells suppressing T helper type 1-mediated hepatitis.
BACKGROUND
Recently, we found that portal vein tolerance is associated with generation of Th2 cells and apoptosis of Th1 cells in the liver, which is regulated by antigen (Ag)-presenting dendritic cells (DCs) in the periportal area and sinusoids.


OBJECTIVE
In this study, we tested whether the periportal and sinusoidal DCs, which were loaded with an Ag in vivo, can inhibit liver injury caused by Th1 cells activated by the Ag administered systemically.


METHODS
Ag-specific hepatitis model was created by adoptively transferring ovalbumin (OVA)-specific CD4(+) T cells to BALB/c mice and venous injection of OVA-containing liposomes. Liver CD11c(+) cells obtained from mice fed OVA were then transferred into these mice.


RESULTS
The transfer of liver CD11c(+) cells from OVA-fed mice completely inhibited hepatic injury, which was associated with apoptosis of OVA-specific CD4(+) T cells and emergence of Th2 cells in the liver. Transfer of CD11c(+) cells and subcutaneous OVA challenge led to enhancement of OVA-specific IgE Ab as well as Th2 cytokine responses in the recipient mice.


CONCLUSIONS
Periportal and sinusoidal DCs loaded with an Ag in the portal vein can induce Th2 response in the liver and prevent hepatic injury caused by Th1 cells.
Watanabe
Tomohiro
T
Department of Clinical Bio-regulatory Science, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.
Katsukura
Hiroaki
H
Chiba
Tsutomu
T
Kita
Toru
T
Wakatsuki
Yoshio
Y
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D039521:CD11c Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011169:Portal Vein / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D039521:CD11c Antigen; D016207:Cytokines; D010047:Ovalbumin