1. ¹Charité-am-MDC, Campus Buch, Berlin, Germany
2. ²Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
3. ³Charité, Campus Benjamin Franklin, Institute for Immunology, Berlin, Germany

Correspondence: Dr S Cayeux, Charité-am-MDC, Max Delbrueck Centrum, Robert Roessle Strasse 10, Berlin 13125, Germany. E-mail: sophie.cayeux@mdc-berlin.de

Received 7 May 2007; Revised 2 July 2007; Accepted 3 July 2007; Published online 16 August 2007.

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-. It appears that splenic CD11c⁺ cells can downregulate splenic specific CD4⁺ T-cell response thereby leading to a decrease in antitumour systemic immunity.