Antigen-presenting cells. Experimental and clinical studies of dendritic cells

We present a summary of our experimental and clinical studies of dendritic cells (DCs) in five different areas. First, human DCs undergo chemotaxis and transendothelial migration in response to distinct chemokines, depending on their maturation state; inducible chemokines may recruit immature DCs to sites of inflammation and infection, whereas constitutive chemokines may regulate subsequent migration to lymphoid tissues. Second, M-tropic but not T-tropic strains of HIV-1 induce and modulate DC chemotaxis in culture; conceivably this may facilitate viral infection and contribute to pathogenesis in vivo. Third, malaria-infected erythrocytes modulate the maturation and inhibit the function of DCs; adhesion of infected erythrocytes to DCs may impart a selective advantage to the parasite by modulating host immunity. Fourth, a phase I clinical trial of DC-based immunotherapy of cancer has been initiated in which autologous DCs are administered directly into metastatic skin lesions; immune responses to a recall antigen, with which the cells were pulsed, were enhanced in several patients. Finally we describe the growth and characterization of a stably immature, maturation-resistant stage of DCs generated from mouse bone marrow that can induce transplantation tolerance in vivo, and outline studies of their capacity to induce responses of transgenic T cells in vivo.