dendritic cells originate from bone marrow progenitors and migrate via the blood, from which they enter and populate most tissues, including peripheral lymphoid tissues, into which they can make direct entry. entry to particular tissues is based on the particular chemokine receptors they express: CCr1, CCr2, CCr5, CCr6, CXCr1, and CXCr2 (not all shown here, for simplicity). Tissue-resident dendritic cells are highly phagocytic via receptors such as dectin-1, deC 205, dC-sIGn, and langerin, and are actively macropinocytic, but they do not express co-stimulatory molecules. They carry most of the different types of Toll-like receptors (TLrs; see the text). at sites of infection, dendritic cells are exposed to pathogens, leading to activation of their TLrs (top panel). TLr signaling causes the dendritic cells to become activated (‘licensed’), which involves induction of the chemokine receptor CCr7 (second panel). TLr signaling also increases the processing of antigens taken up into phagosomes. dendritic cells expressing CCr7 are sensitive to CCL19 and CCL21, which direct them to the draining lymphoid tissue (third panel). CCL19 and CCL21 provide further maturation signals, which result in higher levels of co-stimulatory B7 molecules and MhC molecules. By the time they arrive in the draining lymph node, conventional dendritic cells have become powerful activators of naive T cells but are no longer phagocytic. They express B7.1, B7.2, and high levels of MhC class I and class II molecules, as well as high levels of the adhesion molecules ICaM-1, ICaM-2, LFa-1, and Cd58 (bottom panel).
CCL21 signaling through CCR7 not only induces the migration of dendritic cells into lymphoid tissue, but it also contributes to their enhanced antigen-presenting function (see Fig. 9.17, third panel). By the time activated dendritic cells arrive within lymphoid tissues, they are no longer able to engulf antigens by phagocytosis or macropinocytosis. They instead express very high levels of long-lived MHC class I and MHC class II molecules, which enable them to stably present peptides from pathogens already taken up and processed. Of equal importance, they express high levels of co-stimulatory molecules on their surface. There are two main co-stimulatory molecules: the structurally related transmembrane glycoproteins B7.1 (CD80) and B7.2 (CD86), which deliver co-stimulatory signals by interacting with receptors on naive T cells (see Section 7-21). Activated dendritic cells also express very high levels of adhesion molecules, including DC-SIGN, and they secrete the chemokine CCL19, which specifically attracts naive T cells. Together, these properties enable the dendritic cell to stimulate strong responses in naive T cells (see Fig. 9.17, bottom panel).