Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs

Abstract

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)-α, 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-α 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.

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…CXCL12 may also have a role in the development of PDCs in bone marrow stromal cell niches [39]. Under reactive conditions, additional molecules are involved in mouse PDCs homing to lymph nodes, such as E-selectin and the chemokine receptors CCR5 and CXCR3 [36,37,40]. Consistent with in vivo data, mouse PDCs migrate in vitro in response to CCL3 and CCL5, and to CXCL9 and CXCL10, the respective CCR5 and CXCR3 ligands.…”

Probing in vivo dendritic cell functions by conditional cell ablation

“…This is highlighted by the fact that the in vivo depletion of LN pDCs impairs the capacity of cDCs to stimulate cytotoxic anti-HSV CD8 + T-cell responses. 87 The pivotal role of pDCs in antiviral immune responses and type I IFN production is well established. In contrast, the ability of pDCs to function as APCs in the priming of naive T cells has, despite their classification as DCs, remained under debate.…”

Plasmacytoid Dendritic Cells Synergize with Myeloid Dendritic Cells in the Induction of Antigen-Specific Antitumor Immune Responses

“…Moreover, it has been suggested that dendritic cell (DC) subsets may interact in the development of antiviral immunity and autoimmune disease (15,16). For example, pDC have been implicated in myeloid DC (mDC) differentiation in systemic lupus erythematosus patients (15).…”