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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1298-1305. Prepublished online as a Blood First Edition Paper on April 18, 2006; DOI 10.1182/blood-2005-11-008615. This Article Full Text (PDF) All Versions of this Article: blood-2005-11-008615v1 108/4/1298    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maksimow, M. Articles by Hanninen, A. Search for Related Content PubMed PubMed Citation Articles by Maksimow, M. Articles by Hanninen, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 11, 2005 Accepted April 4, 2006 Antigen targeting to endosomal pathway in dendritic cell vaccination activates regulatory T cells and attenuates tumor-immunity Mikael Maksimow, Mari Miiluniemi, Fumiko Marttila-Ichihara, Sirpa Jalkanen, and Arno Hanninen* MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, Finland * Corresponding author; email: arno.hanninen{at}utu.fi. Lymphoma cells are malignant cells of the T- or B-cell lineage which often express many surface markers inappropriately, yet are not recognized as abnormal by the immune system. We modeled this situation by inoculating ovalbumin-expressing E.G7-OVA lymphoma cells into mice that expressed ovalbumin as a self-antigen in pancreatic islets, and investigated the efficacy of dendritic cell (DC) vaccination in these mice. Although vaccination with DC expressing ovalbumin induced strong cytotoxic T-cell immunity which led to clearance of E.G7- OVA lymphoma cells in naive C57BL/6 mice, DC vaccination was ineffective in mice expressing ovalbumin as a self- antigen. Antigen modification to increase its processing via the endosomal processing pathway dramatically increased CD4 T cell activation but paradoxically, impaired the protective effect of DC vaccination even in naive mice. Depletion of CD25+ T cells (regulatory T cells, Treg) prior to vaccination restored the efficacy of DC vaccination and allowed eradication of lymphoma also in mice expressing ovalbumin as a self-antigen. We conclude that lymphoma cells may be eradicated using DC vaccination if activation of CD25+ Treg is simultaneously inhibited, and that intentionally enhanced endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell help towards stimulation of Treg. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Berraondo, C. Nouze, X. Preville, D. Ladant, and C. Leclerc Eradication of Large Tumors in Mice by a Tritherapy Targeting the Innate, Adaptive, and Regulatory Components of the Immune System Cancer Res., September 15, 2007; 67(18): 8847 - 8855. [Abstract] [Full Text] [PDF]

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