Dendritic Cells: Unique Leukocyte Populations Which Control the Primary

The description of skin dendritic cells (DC) by Langerhans Nor will dendritic epithelial cells, a specialized subset of T lymphocytes with extensive membrane processes, which are in 1868 was followed by prolonged speculation as to their function. Steinman and Cohn identified mouse spleen DC in found in epithelial surfaces in mice but are rare in humans. Myeloid DC should be further distinguished from thymic 1973 and initiated a series of experiments that established lymphoid tissue–derived DC as potent stimulators of primary DC, which appear to derive from a lymphoid stem cell. Thymic DC (and perhaps other lymphoid lineage–derived immune responses. The observation that similar cells were DC) have an entirely different role; they delete maturing present in the nonlymphoid tissues of both rodents and huT lymphocytes and the prediction that they may have differmans, combined with early evidence that they played an ent properties from the myeloid-derived DC, although conimportant role in heart and kidney transplant rejection, troversial, has received experimental support. generated further interest in DC. However, a paucity of markThe cardinal properties of the myeloid lineage–derived ers for DC, the difficulty distinguishing DC from monocytes/ DC (hereafter DC) include (1) the ability to take up, process, macrophages (Mo/MØ), and the problems involved in purifyand present Ag; (2) the ability to migrate selectively through ing DC made for slow progress. Nonetheless, several laboratissues; and (3) the ability to interact with, stimulate, and tories persisted with their investigations, leading to the current direct T-lymphocyte responses. DC may be the only cell acceptance that DC represent discrete leukocyte population(s) capable of stimulating a naive T lymphocyte but other ‘‘nonof specialist or ‘‘professional’’ antigen presenting cells (APC), professional’’ APC (and DC) can stimulate experienced (acwith an extraordinary capacity for initiating primary (and sectivated or memory) T lymphocytes. As such, DC have unique ondary) T-lymphocyte responses. cell interaction capabilities, some of which relate to their It is now possible to grow DC-like cells in culture and extensive cell membrane processes that are acquired late the first monoclonal antibodies (MoAbs) that react with during DC differentiation/activation (Fig 1). DC have been human DC are available. DC migration is probably directed defined, as of necessity, by these specialized functional charby a range of mediators and recent data suggest that reciproacteristics to distinguish them from Mo and MØ. cal T-lymphocyte feedback provides antigen (Ag)-specific control of DC Ag presentation. This new understanding TOWARD A DEFINITION OF DC of DC function may provide opportunities for therapeutic The Existence of a Lineage? intervention in bone marrow transplantation (BMT), solid organ transplantation, and autoimmune disease. Protocols The original description of mouse spleen DC drew attenfor clinical immunotherapy programs, targeted on malignant tion to their irregular shape with numerous cell membrane cell Ag or infectious agents, are being designed to exploit DC processes, including spiny dendrites, bulbous pseudopods, as ‘‘nature’s adjuvant’’ for optimal therapeutic vaccination. A practical issue facing hematologists is the lack of a clear definition of a DC. This, combined with uncertainty as From the Haematology/Immunology/Transfusion Medicine Reto the ontogeny of DC, limited data as to the interrelationship search Group, Christchurch School of Medicine/Christchurch Hosof different DC populations, and the fact that activation/ pital, Christchurch, New Zealand. differentiation events may dramatically change the morpholSubmitted October 2, 1996; accepted June 6, 1997. The Haematology/Immunology/Transfusion Medicine Research ogy, molecular expression (phenotype), and function of DC, Grants have been supported by the New Zealand Health Research has created difficulties. This review will concentrate mainly Council, Canterbury Medical Research Foundation, Cancer Society on the myeloid lineage–derived DC, which associate with of New Zealand, Lottery Health Research Council, McClelland T lymphocytes within lymphoid tissue, to provide critical Trust, Leukemia and Blood Foundation of New Zealand, Loch MaAPC activity for initiating specific T-lymphocyte activation ben Trust, University of Otago, and others. and proliferation. Follicular dendritic cells (FDC), Address reprint requests to Derek N.J. Hart, MD, D Phil, Haemawhich are present within the B-lymphoid follicle, do not tology/Immunology/Transfusion Medicine Research Group, Canteroriginate from the BM, have a different phenotype, and retain bury Health Laboratories, PO Box 151, Christchurch, New Zealand. Ag for prolonged periods, thereby restimulating B lymphoq 1997 by The American Society of Hematology. 0006-4971/97/9009-0051$3.00/0 cytes and perhaps T lymphocytes, will not be reviewed.