The biology and clinical applications of dendritic cells

Dendritic cells (DC) have an essential role in the induction of immune responses to antigen by naive T cells. As 'professional' antigen-presenting cells they are specialized to take up, process and present soluble antigens in complexes with either class I or class II MHC molecules. They are present in only trace numbers in most tissues and in a relatively immature state but, in the presence of inflammatory signals, they rapidly take up foreign antigens and undergo maturation into potent antigen-presenting cells that migrate to secondary lymphoid tissue where they initiate an immune response. It is now possible to expand populations of DC in vitro both from primitive haemopoietic progenitors as well as from more mature peripheral blood mononuclear cells. This has shed light on many developmental aspects of DC biology and furthered our knowledge of the mechanisms of antigen processing and presentation. It is clear that there is more than one pathway of DC differentiation and that some DC may actually induce immunological unresponsiveness--a possible mechanism for tolerance to self-antigens. For clinicians the most exciting prospect is of their use as cellular adjuvants to generate beneficial responses to antigens of low immunogenicity such as tumour antigens. This review outlines aspects of human DC development and the way in which a greater understanding of their biology may lead to promising clinical applications.