[Dendritic cells: a complex cellular system]

Dendritic cells (DC) are the most potent antigen-presenting cells. Thus, ex vivo antigen-pulsed DC are a potentially powerful tool to induce in vivo immunity against tumor-associated or viral antigens. Therefore, culture methods to generate high numbers of DC from bone marrow or blood CD34+ hematopoietic progenitor cells have recently been developed. These methods, which use different combinations of growth factor--mainly granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha and interleukin (IL)-4--make the characterization of DC obtained from CD34+ cells of different origins easier and allow to assess whether DC relate to a unique or distinct differentiation pathways. Monocytes and even macrophages can also directly differentiate into DC in the presence of GM-CSF and IL-4. This has to be reconciled with evidence supporting earlier branching off of the macrophage and DC lineages, and raises questions as to the identity of the latter lineage. Apart from DC of myeloid origin, DC may also originate from lymphoid progenitors. Because the capacity of DC to capture, process and present antigens is known to vary according to their differentiation stage, and lymphoid DC might behave differently from lymphoid DC in this respect, the definition of which type of DC to use for immunotherapy must be more precise, in order to avoid detrimental side effects or results. From a practical point of view, it is also necessary to define the most appropriate cytokine combinations and schedules thereof to optimize proliferation and differentiation of DC from different origins. These conditions should then be applied to generated DC for their efficient and safe use for clinical immunotherapy.