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 Blood, 15 December 2005, Vol. 106, No. 13, pp. 4225-4233.
Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-03-0975.

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IMMUNOBIOLOGY

Immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo

Claus Haase, Mette Ejrnaes, Amy E. Juedes, Tom Wolfe, Helle Markholst, and Matthias G. von Herrath

From the Hagedorn Research Institute, Gentofte, Denmark; the La Jolla Institute for Allergy and Immunology, San Diego, CA; and Novo Nordisk, ImmunoPharmacology, Måløv, Denmark.

In immunotherapy, dendritic cells (DCs) can be used as powerful antigen-presenting cells to enhance or suppress antigen-specific immunity upon in vivo transfer in mice or humans. However, to generate sufficient numbers of DCs, most protocols include an ex vivo culture step, wherein the cells are exposed to heterologous serum and/or antigenic stimuli. In mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immature DCs generated in the presence of IL-10 by comparing fetal bovine serum (FBS)- or normal mouse serum (NMS)-supplemented DC cultures. We show that FBS-exposed DCs induce a systemic immune deviation characterized by reduction of virus-specific T cells, delayed viral clearance, and enhanced systemic production of interleukin 4 (IL-4), IL-5, and IL-10 to FBS-derived antigens, including bovine serum albumin (BSA). By contrast, DCs generated in NMS-supplemented cultures modulated immunity and autoimmunity in an antigen-specific fashion. These cells did not induce systemic IL-4, IL-5, or IL-10 production and inhibited generation of virus-specific T cells or autoimmunity only if pulsed with a viral antigen. These data underscore the importance of using autologous serum-derived immature DCs in preclinical animal studies to accurately assess their immunomodulatory potential in future human therapeutic settings, where application of FBS is not feasible.


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