Blood, 1 May 2003, Vol. 101, No. 9, pp. 3342-3342
Plasmacytoid dendritic cells: are they professional antigen-presenting cells?
Interferon-producing cells (IPCs) are a small subset of
human blood leukocytes that secrete high levels of type I interferons (type I IFN, ie, IFN-
and -
) in response to viruses. Recently, it
was shown that IPCs correspond to a unique dendritic cell (DC) subset,
called plasmacytoid dendritic cells (pDCs), based on their plasma
cell-like morphology, cell-surface expression of MHC-II, and capacity
to stimulate proliferation and differentiation of allogeneic helper T
cells. Establishing the identity of IPCs and pDCs has revived interest
in the immune functions of these cells. One fundamental
question in particular is: can pDCs present specific antigens?
In this issue, Fontaneau and colleagues (page 3520) address this
question and show that pDCs incubated with influenza virus can present
viral antigens on MHC-I and MHC-II molecules and efficiently stimulate
influenza virus-specific CD4+ and CD8+ T-cell
clones. Thus, pDCs do indeed present antigens, at least to memory T
cells, as do conventional DCs. But do pDCs present antigens
differently than other DCs? Fontaneau et al show that pDCs are more
resistant than DCs to the cytopathic effects of influenza virus
infection. This is consistent with the production of high levels of
type I INF by pDC. Consequently, antigen presentation by pDC may be
more sustained and effective than that mediated by conventional DC
during viral infections. In addition, type I IFN secretion by pDCs
may protect bystander DCs, thereby augmenting the overall presentation
of viral antigens.
Another distinctive feature of pDCs, underscored by Fontaneau et al's
study, is the capacity to efficiently induce differentiation of
influenza virus-specific T cells into IFN-
-producing T cells. pDCs specialize in promoting Th1 responses against intracellular pathogens through the secretion of multiple Th1-polarizing
cytokines including IFN-, IL-12, and IL-23. The predominant role of
pDCs in proinflammatory responses against intracellular pathogens is emphasized by the demonstration that pDCs secrete the proinflammatory chemokines IL-8, CCL3 (MIP-1), and CXCL10 (IP-10), which attract Th1-type cells. In contrast, DCs preferentially secrete CCL22 (MDC),
which attracts T cells with a Th2 phenotype as well as CD4+CD25+ regulatory T cells.
Altogether, this study suggests that pDCs and DCs are functionally
distinct antigen-presenting cells that cooperate during an immune
response, promoting the rapid generation of an effective response to
pathogens while preserving tolerance to self-antigens.
Marco Colonna
Washington University School of
Medicine
