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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.
Submitted March 10, 2005
Hagedorn Research Institute, Gentofte, Denmark; ImmunoPharmacology, Novo Nordisk A/S, Malov, Denmark * Corresponding author; email: hmar{at}hagedorn.dk.
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 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 produc-tion of IL-4, IL-5 and IL-10 to FBS-derived antigens, including 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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