Virus-stimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells
Open Access
- 1 February 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 107 (3), 1031-1038
- https://doi.org/10.1182/blood-2005-04-1737
Abstract
Immune responses to pathogens need to be maintained within appropriate levels to minimize tissue damage, whereas such controlled immunity may allow persistent infection of certain types of pathogens. Interleukin 10 (IL-10) plays an important role in such immune regulation. We previously showed that HSV-stimulated human plasmacytoid dendritic cells (pDCs) induced naive CD4+ T cells to differentiate into interferon γ (IFN-γ)/IL-10–producing T cells. Here we show that HSV-stimulated pDCs induce allogeneic naive CD4+ T cells to differentiate into cytotoxic regulatory T cells that poorly proliferate on restimulation and inhibit proliferation of coexisting naive CD4+ T cells. IL-3–stimulated pDCs or myeloid DCs did not induce such regulatory T cells. Both IFN-α and IL-10 were responsible for the induction of anergic and regulatory properties. High percentages of CD4+ T cells cocultured with HSV-stimulated pDCs, and to a lesser extent those cocultured with IL-3–stimulated pDCs, expressed granzyme B and perforin in an IL-10–dependent manner. CD4+ T cells cocultured with HSV-stimulated pDCs accordingly exhibited cytotoxic activity. The finding that virus-stimulated pDCs are capable of inducing CD4+ cytotoxic regulatory T cells suggests that this DC subset may play an important role in suppressing excessive inflammatory responses and also in inducing persistent viral infection.This publication has 44 references indexed in Scilit:
- Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled AntigenThe Journal of Experimental Medicine, 2004
- Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic CellsThe Journal of Experimental Medicine, 2003
- Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic CellsThe Journal of Experimental Medicine, 2002
- The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti–IL-10 Receptor Antibody for Sterile CureThe Journal of Experimental Medicine, 2001
- Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial AntigensThe Journal of Experimental Medicine, 2001
- Identification of CpG oligonucleotide sequences with high induction of IFN-α/β in plasmacytoid dendritic cellsEuropean Journal of Immunology, 2001
- Natural Interferon α/β–Producing Cells Link Innate and Adaptive ImmunityThe Journal of Experimental Medicine, 2000
- Perforin Gene Defects in Familial Hemophagocytic LymphohistiocytosisScience, 1999
- CD4+ T Cell Clones Producing both Interferon-γ and Interleukin-10 Predominate in Bronchoalveolar Lavages of Active Pulmonary Tuberculosis PatientsClinical Immunology, 1999
- Functional Role of Type I and Type II Interferons in Antiviral DefenseScience, 1994