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

Gene Therapy volume 14, pages 1481–1491 (2007)Cite this article

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 OVA323–339 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.

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Acknowledgements

We thank Andrea Katzer and Ute Nitschke for excellent technical assistance. This work was supported by Grant 2001.106.1 from the Wilhelm-Sander-Stiftung and by the Deutsche Forschungsgemeinschaft (Transregio-Sonderforschungsprogramm 36 Projekt B2).

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Authors and Affiliations

  1. Charité-am-MDC, Campus Buch, Berlin, Germany

    S Cayeux, B Bukarica, M Bunse & B Dörken

  2. Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    C Buschow, J Charo & T Blankenstein

  3. Charité, Campus Benjamin Franklin, Institute for Immunology, Berlin, Germany

    T Blankenstein

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  1. S Cayeux
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  2. B Bukarica
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Correspondence to S Cayeux.

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Cayeux, S., Bukarica, B., Buschow, C. et al. In vivo splenic CD11c cells downregulate CD4 T-cell response thereby decreasing systemic immunity to gene-modified tumour cell vaccine. Gene Ther 14, 1481–1491 (2007). https://doi.org/10.1038/sj.gt.3303003

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