Modulation of Dendritic Cells for Tolerance Induction*

Dendritic cells (DC) are uniquely well-equipped antigen (Ag) presenting cells that initiate and regulate immune responses. DC play a dualistic role in the regulation of immune responses. They initiate adaptive immunity by the activating naive lymphocytes and are powerful stimulators of natural killer cells – the crucial cellular instigators of the innate immune system. Furthermore, DC induce central and peripheral tolerance by mechanisms such as deletion, anergy and induction of regulatory lymphocytes [1]. Attention has long been focused on the exceptional ability of these professional antigen-presenting cells (APC) to stimulate T-cell and B-cell mediated responses. Recently, evidence has emerged concerning the inherent tolerogenicity of DC in the periphery [2, 3]. Mechanisms whereby DC can promote peripheral tolerance are under intensive investigation. These studies have important implications for the therapy of autoimmune disorders and allograft rejection. DC are extremely well equipped for their role in innate and adaptive immunity. They are unrivaled in their ability to capture macromolecules via macropinocytosis and mannose receptor-mediated endocytosis into intracellular MHC class II-rich compartments [4]. Following Ag uptake and activation, DC migrate from the periphery to secondary lymphoid tissue, redistribute MHC-Ag complexes to the cell Modulation of Dendritic Cells for Tolerance Induction*