Blood, 15 December 2001, Vol. 98, No. 13, pp. 3503-3503
Plasmacytoid dendritic cells: ready to be tested in
vivo
While dendritic cells (DCs) are best known for their
capacity to initiate specific immune responses, more recent findings show that DCs are essential in controlling not only central but also
peripheral tolerance, and that they are closely linked to innate
immunity. Such distinct functions can only be accomplished by adaptive
flexibility and diversification. Indeed, multiple subsets of immature
and mature dendritic cells, distinguishable by surface antigen
expression, localization, and cytokine production, have been described.
One such subset, consisting of the plasmacytoid dendritic cell (DC2)
and its immediate precursor, the plasmacytoid cell (pDC2, or
pre-DC2), was recently characterized in humans. Upon
stimulation, pDC2s produce high amounts of IFN-
/
and can
differentiate in vitro into DC2s that are capable of inducing strong
T-helper cell (Th) responses (reviewed in Liu, Cell.
2001;106:259-262). Subsequent studies showed that pDC2s are mobilized
by G-CSF and Flt3 ligand, and that high numbers in peripheral blood or
marrow grafts potentially limit graft-versus-host disease and are
associated with increased relapse rates after allogeneic
transplantation. PDC2s are susceptible to HIV infection, and their
depletion correlates with disease progression and the occurrence of
opportunistic infections. Accumulation of pDC2/DC2s in allergic and
automimmune lesions was reported, suggesting functional involvement in
these immunologic "hot spots." However, definitive studies have not
been available due to the lack of suitable models.
Björck (page 3520) and Nakano and colleagues (J Exp Med.
2001;194:1171-1178) have now identified a murine cell population resembling the human pDC2/DC2s. These cells possess key pDC2 features including the production of high amounts of IFN- upon viral
challenge and the differentiation into mature DCs upon IL-3R/CD40
stimulation in vitro. In contrast to their human counterparts, the
murine cells express CD11c, and they can produce IL-12, which is still controversial in human DC2s. Other analogies to human plasmacytoid DCs
regarding Th responses, pattern recognition, and chemokine receptor
expression need to be explored. But irrespective of likely minor
differences, the characterization of murine plasmacytoid DCs provides
the means to rigorously study this cell type. Specifically, it will be
possible to elucidate their lineage origin and developmental pathways
and, more importantly, to clarify their function in immunologic challenges such as infection, autoimmune disease, cancer, and transplantation.
Markus G. Manz
Stanford University School of Medicine
