CD1d-restricted T cells license B cells to generate long-lasting cytotoxic antitumor immunity in vivo.
Although resting B cells are known for being poorly immunogenic and for inducing T-cell tolerance, we have here attempted to test whether their immunogenicity could be enhanced by CD1d-restricted invariant T cells (iNKT) to a point where they could be used in cellular vaccines. We found that the addition of the iNKT ligand alpha-galactosylceramide (alphaGalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CTL immunity. This CTL was induced independently of CD4 T and natural killer cells but required iNKT and CD8 T cells. B cells directly primed CTL, and the alphaGalCer and the peptide must be presented on the same cell. Importantly, our B-cell-based vaccine is comparable in efficiency with dendritic cell-based vaccines, inducing similar CTL responses as well as providing an effective regimen for preventing and suppressing s.c. and metastatic tumors. Therefore, with the help of iNKT, peptide-pulsed B cells can establish long-lasting antitumor immunity and so show promise as the basis for an alternative cell-based vaccine.
Chung
Yeonseok
Y
Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shillim-9-dong, Kwanak-gu, Seoul 151-742, Korea.
Kim
Byung-Seok
BS
Kim
Yeon-Jeong
YJ
Ko
Hyun-Jeong
HJ
Ko
Sung-Youl
SY
Kim
Dong-Hyeon
DH
Kang
Chang-Yuil
CY
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide