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-α and -β) 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-γ–producing T cells. pDCs specialize in promoting Th1 responses against intracellular pathogens through the secretion of multiple Th1-polarizing cytokines including IFN-α, 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-1α), 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.
