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  • Title: In vivo splenic CD11c cells downregulate CD4 T-cell response thereby decreasing systemic immunity to gene-modified tumour cell vaccine.
    Author: Cayeux S, Bukarica B, Buschow C, Charo J, Bunse M, Dörken B, Blankenstein T.
    Journal: Gene Ther; 2007 Oct; 14(20):1481-91. PubMed ID: 17700709.
    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.
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