Some interfaces of dendritic cell biology.

The field of dendritic cell (DC) biology is robust, with several new approaches to analyze their role in vivo and many newly recognized functions in the control of immunity and tolerance. There also is no shortage of mysteries and challenges. To introduce this volume, I would like to summarize four interfaces of DC research with other lines of investigation and highlight some current issues. One interface is with hematopoiesis. DCs constitute a distinct lineage of white blood cell development with some unique features, such as their origin from both lymphoid and myeloid progenitors, the existence of several distinct subsets, and an important final stage of differentiation termed "maturation," which occurs in response to inflammation and infection, and is pivotal for determining the subsequent immune response. A second interface is with lymphocyte biology. DCs are now known to influence many different classes of lymphocytes (B, NK, NKT) and many types of T cell responses (Th1/Th2, regulatory T cells, peripheral T cell deletion), not just the initial priming or induction of T cell-mediated immunity, which was the first function to be uncovered. DCs are sentinels, controlling many of the afferent or inductive limbs of immune function, alerting the immune system and controlling its early decisions. A third interface is with cell biology. This is a critical discipline to understand at the subcellular and molecular levels the distinct capacities of DCs to handle antigens, to move about the body in a directed way, to bind and activate lymphocytes, and to exert many quality controls on the type of responses, for both tolerance and immunity. A fourth interface is with medicine. Here DCs are providing new approaches to disease pathogenesis and therapy. This interface is perhaps the most demanding, because it requires research with humans. Human research currently is being slowed by the need to deal with many challenges in the design of such studies, and the need to excite, attract and support the young scientists who are essential to move human investigation forward. Nonetheless, DCs are providing new opportunities to study patients and the many clinical conditions that involve the immune system.