CD8+ T-cell tolerance can be broken by an adenoviral vaccine while CD4+ T-cell tolerance is broken by additional co-administration of a toll-like receptor ligand

V. Salucci, C. Mennuni, F. Calvaruso, R. Cerino, P. Neuner, G. Ciliberto, N. La Monica, E. Scarselli

Research output: Contribution to journalArticlepeer-review

Abstract

T-cell tolerance to tumor antigens is a considerable challenge to cancer immunotherapy. The existence of a murine model transgenic for human carcinoembryonic antigen (CEA) allows CEA vaccination efficacy to be studied in a physiologically tolerant context. Immunization of CEA-transgenic mice with an adenoviral vector coding for CEA induced a significant CD8+ T-cell response specific to CEA but failed to induce CEA-specific CD4+ T cells and antibodies. To overcome CD4+ T-cell tolerance, we explored the effect of adjuvants inducing in vivo dendritic cell maturation. Two different Toll-like receptor ligands, monophosphoryl lipid A (MPL) and CpG motif-containing oligodeoxynucleotides (CpG-ODN), were tested. CD4 +-mediated IFN-γ production was induced in the CEA-transgenic mice only when the genetic immunization was performed in the presence of these adjuvants. Moreover, CpG-ODN had a greater effect than MPL in inducing CD4 + T-cell response and enabling anti-CEA antibody production.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalScandinavian Journal of Immunology
Volume63
Issue number1
DOIs
Publication statusPublished - Jan 2006

ASJC Scopus subject areas

  • Immunology

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