Dendritic cells and the control of immunity

Abstract

Bone marrow-derived dendritic cells are potent stimulators of several subsets of lymphocytes, including CD4+, CD8+ and NK T cells. One approach to demonstrating the adjuvant role of dendritic cells is to expand them ex vivo, charge the cells with antigens, and then reinfuse the dendritic cells into autologous recipients to initiate immunity. Several groups are currently testing if this approach can elicit immunity to tumor antigens in humans. Recent studies have emphasized the control of dendritic cell function per se, i.e., the requirements for developing potent antigen-presenting cells from less active precursors. A key step is termed maturation. Using model peptides and proteins, we find that dendritic cells must receive a maturation stimulus to optimally present antigens as MHCpeptide complexes. Maturation in addition permits irreversible differentiation to motile cells that express high levels of IL-12 and several costimulatory molecules such as CD40 and CD86. Dendritic cells also efficiently process and present peptides derived from other apoptotic cells, including tumor cells. Dendritic cell maturation is likely to be a pivotal control point in the initiation of immunity, since it allows for efficient antigen presentation and the acquisition of several other functions pertinent to stimulating T cells in situ.