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      1. Author :
      2. Title :
      3. Type :
        Journal Article
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      11. Keywords :
        Adoptive Transfer; Animals; Antigen Presentation; Autoantigens; B16-F10-luc-G5 cells; Bioware; Cancer Vaccines; dendritic cells; Endosomes; Lymphocyte Activation; Lymphoma; Mice; Mice, Knockout; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Vaccination
      12. Abstract :
        Lymphoma cells are malignant cells of the T- or B-cell lineage that 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 [Tregs]) 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(+) Tregs is simultaneously inhibited, and that intentionally enhanced endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell help toward stimulation of Tregs.
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      14. Call Number :
        PKI @ catherine.lautenschlager @
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