Schlecht, G. et al. Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation. Blood 104, 1808−1815

Unité de Biologie des Régulations Immunitaires, Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France.
Blood (Impact Factor: 10.45). 10/2004; 104(6):1808-15. DOI: 10.1182/blood-2004-02-0426
Source: PubMed


Like their human counterparts, mouse plasmacytoid dendritic cells (pDCs) play a central role in innate immunity against viral infections, but their capacity to prime T cells in vivo remains unknown. We show here that virus-activated pDCs differentiate into antigen-presenting cells able to induce effector/memory CD8(+) T-cell responses in vivo against both epitopic peptides and endogenous antigen, whereas pDCs activated by synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG) acquire only the ability to recall antigen-experienced T-cell responses. We also show that immature pDCs are unable to induce effector or regulatory CD8(+) T-cell responses. Thus, murine pDCs take part in both innate and adaptive immune responses by directly priming naive CD8(+) T cells during viral infection.

Download full-text


Available from: Antonio A Freitas
  • Source
    • "Moreover, several studies reported that pDCs are able to prime potent melanoma-specific CD8+ T cells, which produce IFN-γ and are able to locate to melanoma lesions (108, 120, 138, 139). Finally, pre-clinical mouse models showed that pDCs are able to induce a tumor-specific T cell response in vivo, leading to control of tumor growth (138, 140). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cell (DC)-based immunotherapy employs the patients' immune system to fight neoplastic lesions spread over the entire body. This makes it an important therapy option for patients suffering from metastatic melanoma, which is often resistant to chemotherapy. However, conventional cellular vaccination approaches, based on monocyte-derived DCs (moDCs), only achieved modest response rates despite continued optimization of various vaccination parameters. In addition, the generation of moDCs requires extensive ex vivo culturing conceivably hampering the immunogenicity of the vaccine. Recent studies, thus, focused on vaccines that make use of primary DCs. Though rare in the blood, these naturally circulating DCs can be readily isolated and activated thereby circumventing lengthy ex vivo culture periods. The first clinical trials not only showed increased survival rates but also the induction of diversified anti-cancer immune responses. Upcoming treatment paradigms aim to include several primary DC subsets in a single vaccine as pre-clinical studies identified synergistic effects between various antigen-presenting cells.
    Full-text · Article · Apr 2014 · Frontiers in Immunology
  • Source
    • "Intracellularly Ag derived peptides either expressed by the cell itself (Krug et al., 2003; Young et al., 2008) or derived from intracellular-virus (Fonteneau et al., 2003; Salio et al., 2004; Schlecht et al., 2004; McGill et al., 2008; Young et al., 2008) are efficiently presented by pDCs through MHCI. Whether pDCs can phagocytose bacteria is still unclear (Villadangos and Young, 2008), while they have been shown to endocytose virions and exogenous proteins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasmacytoid dendritic cells (pDCs) are a particular subset of DCs that link innate and adaptive immunity. They are responsible for the substantial production of type 1 interferon (IFN-I) in response to viral RNA or DNA through activation of TLR7 and 9. Furthermore, pDCs present antigens (Ag) and induce naïve T cell differentiation. It has been demonstrated that pDCs can induce immunogenic T cell responses through differentiation of cytotoxic CD8(+) T cells and effector CD4(+) T cells. Conversely, pDCs exhibit strong tolerogenic functions by inducing CD8(+) T cell deletion, CD4(+) T cell anergy, and Treg differentiation. However, since IFN-I produced by pDCs efficiently activates and recruits conventional DCs, B cells, T cells, and NK cells, pDCs also indirectly affect the nature and the amplitude of adaptive immune responses. As a consequence, the precise role of Ag-presenting functions of pDCs in adaptive immunity has been difficult to dissect in vivo. Additionally, different experimental procedures led to conflicting results regarding the outcome of T cell responses induced by pDCs. During the development of autoimmunity, pDCs have been shown to play both immunogenic and tolerogenic functions depending on disease, disease progression, and the experimental conditions. In this review, we will discuss the relative contribution of innate and adaptive pDC functions in modulating T cell responses, particularly during the development of autoimmunity.
    Full-text · Article · Mar 2013 · Frontiers in Immunology
  • Source
    • "Salio et al. [23] proposed that high numbers of peptide-pulsed pDCs are equally efficient as peptide-pulsed mDCs in priming of CD8+ T cells. This notion is supported by the finding that murine pDCs exposed to influenza virus induced the generation of memory CD8+ T cells as well as effector CD8+ T cells upon rechallenge with the virus, leading to protective immunity [20]. Further evidence that pDCs can induce protective immunity comes from studies where mice were vaccinated with CpG-matured tumor peptide-pulsed pDCs or pulsed by a Leishmania major (L. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The plasmacytoid dendritic cell (pDC) constitutes a unique DC subset that links the innate and adaptive arm of the immune system. Whereas the unique capability of pDCs to produce large amounts of type I IFNs in response to pathogen recognition is generally accepted,their antigen-presenting function is often neglected since most studies on antigen presentation are aimed at other DC subsets. Recently, pDCs were demonstrated capable to present antigen leading to protective tumor immunity. In this review, we discuss how pDCs could be exploited in the fight against cancer by analyzing their capacity to capture,process and (cross-) present antigen.
    Full-text · Article · Feb 2012 · Cancer Immunology and Immunotherapy
Show more