Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2-and CD40L-dependent manner. pDC-derived IFN-further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.

Viruses have evolved a variety of mechanisms to evade the immune system, invade host tissues, and, sometimes, establish persistent infections (1). One strategy by which hosts counter these assaults is the rapid response of the DC network to eliminate virally infected cells. In mice, there are at least three major functional subtypes of DCs in LNs: myeloid DCs (mDCs; CD11b B220–CD11c), CD8 DCs (CD8 B220–CD11c), and plasmacytoid DCs (pDCs; B220 CD11c), which induce distinct types of antiviral T lymphocytes (2, 3). This heterogeneity in the DC network allows flexibility in the immune response, depending on the tissue environment and exogenous factors in LNs (2, 4). In HSV-2 infections of the vaginal submucosa, newly recruited mDCs induce virusspecific T helper cells (5), whereas in cutaneous HSV-1 infections, CD8 DCs, which mainly reside in LNs, are responsible for crosspriming antiviral CTLs (6). In contrast, pDCs function poorly as APCs for naive T cells, but produce large amounts of antiviral IFN-.