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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Akira
A
Sasakawa
Tomohide
T
Tatsumi
Tetsuo
T
Takehara
Shinjiro
S
Yamaguchi
Masashi
M
Yamamoto
Kazuyoshi
K
Ohkawa
Takuya
T
Miyagi
Norio
N
Hayashi
D000818:Animals; D017951:Antigen Presentation; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology*; D007167:Immunotherapy; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013160:Splenic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
D016207:Cytokines; D005699:Galactosylceramides; D016159:Tumor Suppressor Protein p53; C493154:alpha-galactosylceramide