In vivo priming of natural killer T cells by dendritic cells pulsed with hepatoma-derived acid-eluted substances.
Many murine tumor cells express not only individual haplotype-matched class I MHC molecules, but also species-specific CD1d molecules. The former class I MHC molecules generally present internally synthesized tumor-derived peptide antigens to highly specific CD8(+) cytotoxic T lymphocytes (CTLs) in acquired immunity. In contrast, the latter CD1d molecules may present tumor-associated glycolipid antigens to broadly crossreactive natural killer T (NKT) cells, which might correlate with controlling tumor metastasis. Here, we showed that murine hepatoma cell line Hepa1-6-derived acid-eluted substances might contain both D(b) class I MHC-restricted antigens and CD1d-restricted substances, which could sensitize not only syngeneic bone marrow-derived DCs (BM-DCs), but also allogeneic BM-DCs expressing haplotype-mismatched class I MHC and species-specific CD1d molecules. To our surprise, intravenous (i.v.) immunization of C57BL/6 mice with the former syngeneic BM-DCs carrying acid-eluted materials primed both CD4(-)CD8(-) and CD8(+) NKT cells in the spleen, whereas immunization with the latter allogeneic BM-DCs loaded the tumor-derived substances primed CD4(-)CD8(-), but not CD8(+) NKT cells. The findings shown in the present study will open a new area for cancer immunotherapy using allogeneic DCs and tumor-derived acid-eluted substances.
Ishii
Ritsuko
R
Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602, Tokyo, Japan.
Shimizu
Masumi
M
Nakagawa
Yohko
Y
Shimizu
Kazuo
K
Tanaka
Shigeo
S
Takahashi
Hidemi
H
D000143:Acids / Q000737:chemistry; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000502:physiology*; D007114:Immunization; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured
D000143:Acids; D018949:Antigens, CD1; D055610:Antigens, CD1d; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments