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J Hepatol. 2009 Jun;50(6):1155-62. doi: 10.1016/j.jhep.2008.12.027. Epub 2009 Feb 26.

Activated liver dendritic cells generate strong acquired immunity in alpha-galactosylceramide treatment.

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Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.



Alpha-galactosylceramide (alpha-GalCer) presented by dendritic cells (DCs) activates NKT cells that in turn drive DC maturation. However, the potential of generating acquired immunity of liver DCs in alpha-GalCer treatment remains unclear.


We examined the activation of acquired immunity in the alpha-GalCer treatment against liver or spleen tumor and the ability of liver and spleen DCs in the generation of acquired immunity.


Administration of alpha-GalCer resulted in generation of p53 peptide-specific cytotoxic T lymphocytes (CTLs) in mice bearing liver CMS4 tumor, aberrantly expressing p53, but not in mice bearing spleen CMS4 tumor. The growth of rechallenged CMS4 subcutaneous tumor was inhibited in alpha-GalCer-treated mice against liver CMS4 tumor, but not in alpha-GalCer-treated mice against CMS4 spleen tumor. The antigen presenting related functions of liver DCs were significantly higher than those of spleen DCs in alpha-GalCer-treated mice. Vaccination of normal mice with p53 peptide pulsed liver DCs isolated from alpha-GalCer treated mice resulted in generation of p53 peptide-specific CTLs, but that with p53 peptide pulsed spleen DCs did not.


These results demonstrated that alpha-GalCer treatment induced unique immunologic activation of liver DCs in comparison with spleen DCs, which might be favorable to generate liver acquired immunity.

[Indexed for MEDLINE]

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