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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

2004; Wiley; Volume: 34; Issue: 5 Linguagem: Inglês

10.1002/eji.200324368

1521-4141

Kristina Eriksson, Jia‐Bin Sun, Inger Nordström, Margareta Fredriksson, Marianne Lindblad, Bin‐Ling Li, Jan Holmgren,

Escherichia coli research studies

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.