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Dendritic cells (DCs) are currently considered as promising tools for vaccination against tumors and also autoimmune responses. A major point of concern has been the use of fetal calf serum (FCS) as a source of heterologous antigen in DC cultures. FCS peptides can be presented by the DCs and cause T-cell responses in the recipient. We investigated the role of FCS in an autoimmune model where DC injections can prevent peptide-specifically from experimental autoimmune encephalomyelitis (EAE). We show that murine bone marrow-derived DCs generated in FCS-containing or serum-free media resulting in a similar phenotype, maturation potential, and functions. Peptide-specific protection could be achieved similarly with FCS-DC or serum-free DCs. Although FCS-DC induced strong CD4 T cell proliferation and cytokine production against FCS, these T cells lack antigenic recall during EAE. Even if FCS was reinjected, the effect on EAE resulted only in a 3-day delay of disease onset. Together, our data show that presentation of bystander antigens by peptide-specific DC vaccinations may have little influence on T-cell responses in vivo if the bystander antigen cannot be recalled by specific T cells.

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Denileukin diftitox, also known as DAB389IL-2 or Ontak, is a fusion protein toxin consisting of the full-length sequence of the IL-2 protein and as toxophore the truncated diphtheria toxin. As a consequence, it delivers the toxic agent to CD25-bearing cells, whereby CD25 represents the high-affinity α-subunit of the IL-2 receptor. Initially it was developed for the treatment of patients with cutaneous T cell lymphoma. Meanwhile, denileukin diftitox is also used as an adjuvant in other tumor therapies and neoplastic disorders. In this study, to our knowledge we report for the first time that denileukin diftitox has also dramatic effects regarding the pathology of type 1 diabetes using the NOD mouse model. Repeated injections of denileukin diftitox into female NOD mice at 12 wk of age led to a clear acceleration of disease onset, whereas injection at 7 wk of age did not. Using male NOD mice, which are much less susceptible to diabetes, we demonstrate that the injection of denileukin diftitox leads to a dramatic development of type 1 diabetes within days after injection, thereby obviously breaking pre-existing tolerance mechanisms. This is accompanied by an increased IFN-γ production of autoreactive splenic cells and a decreased presence of regulatory CD4+CD25+Foxp3+ T cells. In contrast, transfer of CD4+CD25+Foxp3+ T cells could correct the defect after denileukin diftitox treatment. Furthermore, whereas IFN-γ production was increased in the pancreata of treated animals, insulin expression was strongly reduced. These finding should be considered when denileukin diftitox is used for the treatment of patients suffering from tumors and/or autoimmune disorders.