Plasmacytoid dendritic cells: both a turn-on and a turn-off

The hallmark of a dendritic cell (DC) is its capacity to initiate immune responses. Now Ardavı́n and colleagues (page383) provide further information on a DC subset in mice that may naturally regulate or suppress immune responses. Histologists originally described a cell type in human tissues, termed “plasmacytoid T cells,” that was subsequently shown to develop into a (plasmacytoid) DC when isolated and cultured in appropriate conditions (IL-3 plus CD40 ligation). These cells were normally localized to secondary lymphoid tissues but were also present in certain malignancies and some inflammatory conditions.

Only recently has a similar subset of DCs been identified in mice by other investigators. The data presented here are consistent with those of previous reports, but the current paper additionally describes the capacity of these cells to induce regulatory T cells that can suppress immune responses, at least in vitro. In part, this may be ascribed to the fact that the freshly isolated cells lack or have low expression of key costimulatory and MHC class II molecules, although it is currently unclear why they apparently induce regulatory T cells rather than simply inducing T-cell anergy. After stimulation with CpG motifs, these molecules are up-regulated and the cells secrete immune-polarizing cytokines (IL-12 and IL-10), and after viral stimulation they can secrete high levels of type I interferon.

Although there may be species differences, the accumulating data from human and murine studies strongly indicate that plasmacytoid DCs have a remarkable functional plasticity. They may normally be involved in the induction or maintenance of tolerance to self-antigens in the thymus and periphery and can contribute to innate defense against viral infection but can also acquire the ability to initiate adaptive immune responses. Interest in this remarkable cell type is gaining momentum with suggestions that it may be involved in the pathogenesis of conditions such as lupus and with the recent finding that it may be selectively recruited to certain types of tumors. Strategies to exploit or modulate the function of plasmacytoid DCs could thus provide some exciting therapeutic possibilities.