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In vivo splenic CD11c cells downregulate CD4 T-cell response thereby decreasing systemic immunity to gene-modified tumour cell vaccine

Item Type:Article
Title:In vivo splenic CD11c cells downregulate CD4 T-cell response thereby decreasing systemic immunity to gene-modified tumour cell vaccine
Creators Name:Cayeux, S. and Bukarica, B. and Buschow, C. and Charo, J. and Bunse, M. and Doerken, B. and Blankenstein, T.
Abstract:One of the factors influencing the efficacy of tumour cell vaccines is the site of immunization. We have shown previously that gene-modified vaccines delivered directly inside the spleen induced antigen cross-presentation by splenic antigen-presenting cells (not B cells). Here, we examined the interaction between splenic CD11c(+) cells and antigen-specific CD4(+) T cells. We used tumour cells expressing ovalbumin (OVA), a situation where CD4(+) T-cell help is required for the generation of a cytotoxic T lymphocyte response. Using in vivo bioluminescence imaging of luciferase-expressing EL4-OVA cells, we could demonstrate that tumour cells were located exclusively inside the spleen following intrasplenic injection. We showed that after intrasplenic immunization with T/SA-OVA cells, splenic class I(+) class II(+) CD11c(+) cells engulfed and presented in vivo the OVA class I-restricted peptide SIINFEKL. However, in vivo previously adoptively transferred 5,6-carboxy-succinimidyl-fluorescein-ester-labelled transgenic CD4(+)KJI-26(+) cells specific for the class II OVA(323-339) peptide underwent abortive proliferation in the spleen. These CD4(+)KJI-26(+) cells were only transiently activated and produced IL-10 and IL-4 and not IFN-gamma. It appears that splenic CD11c(+) cells can downregulate splenic specific CD4(+) T-cell response thereby leading to a decrease in antitumour systemic immunity.
Keywords:Gene-Modified Tumour Cell Vaccine, Splenic Antigen-Presenting Cells, DC-T-Cell Interaction, Animals, Mice
Source:Gene Therapy
ISSN:0969-7128
Publisher:Nature Publishing Group (U.K.)
Volume:14
Number:20
Page Range:1481-1491
Date:October 2007
Official Publication:https://doi.org/10.1038/sj.gt.3303003
PubMed:View item in PubMed

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