Coupling of antigen to cholera toxin for dendritic cell vaccination promotes the induction of MHC class I-restricted cytotoxic T cells and the rejection of a cognate antigen-expressing model tumor.
We previously demonstrated that cholera toxin (CT) is highly efficient as a combined carrier and adjuvant for dendritic cell (DC) vaccination, inducing strong Th1-dominated B cell and CD4(+) T cell responses. In this study we show that vaccination with DC pre-pulsed ex vivo with CT-conjugated OVA (OVA-CT) gives rise to OVA-specific CD8(+) T cells that produce IFN-gamma and are cytotoxic for OVA-expressing E.G7 tumor cells both in vitro and in vivo. The induction of specific CD8(+) CTL by OVA-CT-treated DC was associated with enhanced presentation of OVA peptide (SIINFEKL) on MHC class I in combination with an overall activation of the pulsed DC. Vaccination of mice with OVA-CT-pulsed DC resulted in rejection of already established MHC class I-positive, MHC class II-negative, OVA-expressing E.G7 tumors in an antigen-specific, CD8(+) T cell-dependent fashion and was associated with high numbers of tumor-infiltrating CD8(+) T cells. Conjugation of antigen to CT facilitated DC uptake of the linked antigen through the GM1 receptor-binding B subunit and induced strong activation-maturation signals through the biologically active A subunit. These results have interesting implications for DC vaccination aimed at inducing CTL immune responses.
Eriksson
Kristina
K
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Gothenberg, Sweden. kristina.eriksson@microbio.gu.se
Sun
Jia-Bin
JB
Nordström
Inger
I
Fredriksson
Margareta
M
Lindblad
Marianne
M
Li
Bin-Ling
BL
Holmgren
Jan
J
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology*; D002772:Cholera Toxin / Q000276:immunology / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000922:Immunotoxins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D000922:Immunotoxins; D014612:Vaccines; D002772:Cholera Toxin