Blood, 15 July 2002, Vol. 100, No. 2, pp. 373-373
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 Ardavín and colleagues (page
383) 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.
Jonathan M. Austyn
University of
Oxford
