Plasmacytoid Dendritic Cells Regulate Th Cell Responses through OX40 Ligand and Type I IFNs

Abstract

Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses. IL-3-treated PDCs expressed OX40L, but produced almost no IFN-α in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. Meanwhile, PDCs were rapidly endowed by viral infection (Sendai virus) with a high potency to develop IFN-γ-producing Th cells depending on their capacity to residually produce IFN-α. Although Sendai virus-stimulated PDCs simultaneously expressed OX40L in their maturational process, the Th1-inducing effect of endogenous type I IFNs may overcome and thus conceal the OX40L-dependent Th2 responses. However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-α-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent. Thus, PDCs have the distinct means to dictate an appropriate response to environmental stimuli.

A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis

“…TNFRSF4 and its ligand, TNFS4, have been reported to inhibit apoptosis in T cells and to enhance Th2 proliferation. 2,27 However, some infectious agents may also induce Th1 proliferation through TNFRSF4 signals. 22,28 In the context of allergy, however, recall responses were shown to be dependent on TNFRSF4 signals in an animal model of asthma.…”

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

“…It has been reported that PDC express OX40L upon stimulation, and that virus-stimulated PDC modulate Th responses via OX40L and IFN-a [60]. However, involvement of OX40L in PDC-mediated activation of NKT cells or CD8 T cells has not been studied.…”

Human Plasmacytoid Dendritic Cells Phagocytose, Process, and Present Exogenous Particulate Antigen

“…The in vivo function of pDCs as APCs remains controversial and functional outcomes of pDC-T cell interactions largely depend on the immunological context of the encounter (47). Activated pDCs have been demonstrated to promote Th1 (31,47) as well as Th2 responses (32,33), underlining their remarkable functional plasticity.…”

“…Activated pDCs have been demonstrated to promote Th1 (31,47) as well as Th2 responses (32,33), underlining their remarkable functional plasticity. The pDCs were shown to prime specific CD4 + and CD8 + lymphocytes against endogenous and exogenous Ags (15,48), viruses (49) and tumor Ags (45).…”