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

@article{citeulike:1477244, abstract = {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. 10.1182/blood-2005-03-0975}, author = {Haase, Claus and Ejrnaes, Mette and Juedes, Amy E. and Wolfe, Tom and Markholst, Helle and von Herrath, Matthias G. }, citeulike-article-id = {1477244}, doi = {10.1182/blood-2005-03-0975}, journal = {Blood}, keywords = {tolerogenic-dcs}, month = {December}, number = {13}, pages = {4225--4233}, posted-at = {2007-07-24 17:07:45}, priority = {2}, title = {Immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo}, url = {http://dx.doi.org/10.1182/blood-2005-03-0975}, volume = {106}, year = {2005} }

TY - JOUR ID - citeulike:1477244 L3 - citeulike-article-id:1477244 TI - Immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo JF - Blood VL - 106 IS - 13 SP - 4225 EP - 4233 N2 - 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. 10.1182/blood-2005-03-0975 KW - tolerogenic-dcs AU - Haase, Claus AU - Ejrnaes, Mette AU - Juedes, Amy AU - Wolfe, Tom AU - Markholst, Helle AU - von Herrath, Matthias PY - 2005/12/15/ UR - http://dx.doi.org/10.1182/blood-2005-03-0975 ER -