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.
Sasakawa
Akira
A
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tatsumi
Tomohide
T
Takehara
Tetsuo
T
Yamaguchi
Shinjiro
S
Yamamoto
Masashi
M
Ohkawa
Kazuyoshi
K
Miyagi
Takuya
T
Hayashi
Norio
N
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