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

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 inter...

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Veröffentlicht in:Gene therapy 2007-10, Vol.14 (20), p.1481-1491
Hauptverfasser: Cayeux, S, Bukarica, B, Buschow, C, Charo, J, Bunse, M, Dörken, B, Blankenstein, T
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Sprache:eng
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Zusammenfassung: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- γ . It appears that splenic CD11c + cells can downregulate splenic specific CD4 + T-cell response thereby leading to a decrease in antitumour systemic immunity.
ISSN:0969-7128
1476-5462
DOI:10.1038/sj.gt.3303003