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Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-06-1867.

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2003-06-1867v1
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Submitted June 11, 2003
Accepted August 4, 2003

Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T cell responses and tumor immunity

Yangbing Zhao, David Boczkowski, Smita K Nair, and Eli Gilboa*

Center for Genetic and Cellular Therapies, Department of Surgery, Duke University Medical Center, Durham, NC, USA

* Corresponding author; email: e.gilboa{at}cgct.duke.edu.

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+ 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.


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