Homing of intravenously and intralymphatically injected human dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells

Dendritic cells (DC) are professional antigen-presenting cells that can be generated in vitro from CD34(+) peripheral blood progenitor cells by recomb inant cytokines. These cells have potential implications for immunotherapeu tic approaches in the treatment of cancer and other diseases. Physiological ly, immature DC in the periphery capture and process antigens, then mature to interdigitating DC and migrate to lymphoid organs, where they activate l ymphocytes. However, it is not known if DC generated in vitro have the capa city to traffic in vivo to the lymphoid tissues, such as spleen and lymph n odes. We have investigated whether human radiolabeled DC differentiated in vitro migrate and localize to lymphoid tissues after intravenous and intral ymphatic injection. The distribution and localization of the DC were evalua ted in five patients with malignant melanoma using serial whole-body gamma camera imaging. Intravenously infused DC demonstrated transient lung uptake followed by localization in the spleen and liver for at least 7 days. DC i njected into a lymphatic vessel at the dorsal foot were rapidly detected in the draining lymph nodes where they remained for more than 24 h. These dat a suggest that DC differentiated in vitro localize preferentially to lympho id tissue, where they could induce specific immune responses.