New insights into the mobilization and phagocytic activity of dendritic cells

• Published in: The Journal of experimental medicine Vol. 183; no. 4; pp. 1287 - 1292
• Main Author: Austyn, J M
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.04.1996
• Subjects: Animals; Cell Movement; Dendritic Cells - immunology; Dendritic Cells - physiology; Liver - cytology; Lymphatic System; Phagocytosis; Rats; Stem Cells
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.183.4.1287

A study published in this issue of The Journal of Experimental Medicine, sheds new light on the behavior and functions of dendritic cells (DC) which play a pivotal role in initiation of T and T-dependent immune responses. The study is important in at least three respects: first, it provides information on recruitment of DC progenitors to a non-lymphoid tissue, the liver; second, it provides evidence that DC have transient phagocytic activity for particulates in vivo, a prerequisite for induction of immune responses against bacteria for example; and third, it defines a migration pathway for DC, that have acquired particulates from the blood, from the liver to draining nodes. To put this paper into context it is necessary to summarize the general consensus of understanding about the DC lineage that has emerged over the past decade or so. DC progenitors that originate from the bone marrow of adult mammals enter the blood and seed non-lymphoid tissues, where they develop into a stage of DC (sometimes referred to as immature DC) with optimal capabilities for antigen uptake and processing, MHC production, and the formation of foreign peptide-MHC complexes ("processing" DC). These cells are localized in epithelia, such as skin epidermis, gut, genito-urinary tract, and the lung and airways, and in the interstitial spaces of many solid organs such as heart and kidney. Inflammatory mediators (cytokines and other agents) then promote their maturation and migration out of non-lymphoid tissues into blood and/or afferent lymph. These migratory cells enter secondary lymphoid tissues where they express newly acquired capabilities for the initiation of primary T and T-dependent immune responses, at least in part due to their expression of costimulatory molecules and synthesis of certain cytokines such as IL-12 ("presenting" DC, sometimes referred to as mature DC). Migratory DC, travelling between non-lymphoid and secondary lymphoid tissues, are generally considered to be undergoing "maturation" from the processing to presenting stages, although maturation is likely to be initiated within non-lymphoid tissues and to continue within secondary lymphoid tissues. At the outset, it is therefore convenient to define four stages of the DC lineage in distinct anatomical compartments: DC progenitors in bone marrow and blood; immature DC at the processing stage in peripheral non-lymphoid organs; migratory DC in the process of maturation in afferent lymph and blood; and mature DC at the presenting stage in secondary lymphoid tissues. Arguably this view is an over-simplification. For example, DC progenitors may enter secondary lymphoid tissues directly; some DC in non-lymphoid tissues may possess a degree of costimulatory activity; some DC in lymphoid tissues may be capable of antigen uptake and processing to some extent; and DC in thymus may play a role in the induction of T cell tolerance to self peptide-MHC complexes. Nevertheless, it provides a useful framework for understanding how, where, and when DC regulate the induction of primary immune responses. It is also important to add that once antigen-specific T cells have been activated by DC, the activated T cells appear not to require the specialized costimulatory signals that are delivered by DC, and may respond to other types of antigen-presenting cell expressing the peptide-MHC complexes for which they are specific.