Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity.
Induction of potent and sustained antiviral or antitumor immunity is dependent on the efficient activation of CD8+ and CD4+ T cells. While dendritic cells constitute a powerful platform for stimulating cellular immunity, presentation of endogenous antigens by dendritic cells transfected with nucleic acid-encoded antigens favors the stimulation of CD8+ T cells over that of CD4+ T cells. A short incubation of mRNA-transfected dendritic cells with antisense oligonucleotides directed against the invariant chain enhances the presentation of mRNA-encoded class II epitopes and activation of CD4+ T-cell responses in vitro and in vivo. Immunization of mice with the antisense oligonucleotide-treated dendritic cells stimulates a more potent and longer lasting CD8+ cytotoxic T-cell (CTL) response and enhances the antitumor efficacy of dendritic cell-based tumor vaccination protocols. Transient inhibition of invariant chain expression represents a simple and general method to enhance the stimulation of CD4+ T-cell responses from endogenous antigens.
Duke Scholars
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Related Subject Headings
- Transfection
- T-Lymphocytes, Cytotoxic
- Oligonucleotides, Antisense
- Neoplasms, Experimental
- Mice, Inbred C57BL
- Mice
- Lymphocyte Activation
- Immunotherapy, Adoptive
- Immunology
- Immunity, Cellular
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transfection
- T-Lymphocytes, Cytotoxic
- Oligonucleotides, Antisense
- Neoplasms, Experimental
- Mice, Inbred C57BL
- Mice
- Lymphocyte Activation
- Immunotherapy, Adoptive
- Immunology
- Immunity, Cellular