Dendritic Cells in the Immune System—History, Lineages, Tissues, Tolerance, and Immunity

The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the “History” section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The “Lineages” section then focuses on five different populations of DCs: two subsets of “classical” DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells. It highlights some cellular and molecular specializations of each, and also notes other DC subsets that have been proposed. The following “Tissues” section discusses the distribution and behavior of different DC subsets within nonlymphoid and secondary lymphoid tissues that are connected by DC migration pathways between them. In the “Tolerance” section, the role of DCs in central and peripheral tolerance is considered, including their ability to drive the differentiation of different populations of regulatory T cells. In contrast, the “Immunity” section considers the roles of DCs in sensing of infection and tissue damage, the initiation of primary responses, the T-cell effector phase, and the induction of immunological memory. The concluding section provides some speculative ideas about the evolution of DCs. It also revisits earlier concepts of generation of diversity and clonal selection in terms of DCs driving the evolution of T-cell responses. Throughout, this review highlights certain areas of uncertainty and suggests some avenues for future investigation.