Cutting Edge: Inhaled Antigen Upregulates Retinaldehyde Dehydrogenase in Lung CD103+ but Not Plasmacytoid Dendritic Cells To Induce Foxp3 De Novo in CD4+ T Cells and Promote Airway Tolerance

AbstractImmune 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.

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ICOS is associated with poor prognosis in breast cancer as it promotes the amplification of immunosuppressive CD4+T cells by plasmacytoid dendritic cells

OncoImmunology ◽

10.4161/onci.23185 ◽

2013 ◽

Vol 2 (3) ◽

pp. e23185 ◽

Cited By ~ 34

Author(s):

Julien Faget ◽

Vanja Sisirak ◽

Jean-Yves Blay ◽

Christophe Caux ◽

Nathalie Bendriss-Vermare ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Dendritic Cells ◽

Cd4 T Cells ◽

Poor Prognosis ◽

Plasmacytoid Dendritic Cells

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MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity

Journal of Experimental Medicine ◽

10.1084/jem.20092627 ◽

2010 ◽

Vol 207 (9) ◽

pp. 1891-1905 ◽

Cited By ~ 93

Author(s):

Magali Irla ◽

Natalia Küpfer ◽

Tobias Suter ◽

Rami Lissilaa ◽

Mahdia Benkhoucha ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Cd4 T Cells ◽

Class Ii ◽

Plasmacytoid Dendritic Cells ◽

T Cell Response ◽

Lymphoid Tissues ◽

Capture Process

Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4+ T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag–specific contacts with CD4+ T cells. These interactions promote the selective expansion of myelin-Ag–specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4+ T cells in vivo.

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Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0505251102 ◽

2005 ◽

Vol 102 (39) ◽

pp. 13974-13979 ◽

Cited By ~ 122

Author(s):

J.-P. Herbeuval ◽

A. W. Hardy ◽

A. Boasso ◽

S. A. Anderson ◽

M. J. Dolan ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cd4 T Cells ◽

Plasmacytoid Dendritic Cells ◽

Type I ◽

Type I Ifn ◽

Hiv 1

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ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells

Cancer Research ◽

10.1158/0008-5472.can-12-2409 ◽

2012 ◽

Vol 72 (23) ◽

pp. 6130-6141 ◽

Cited By ~ 100

Author(s):

Julien Faget ◽

Nathalie Bendriss-Vermare ◽

Michael Gobert ◽

Isabelle Durand ◽

Daniel Olive ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Dendritic Cells ◽

Cancer Progression ◽

Cd4 T Cells ◽

Plasmacytoid Dendritic Cells ◽

Breast Cancer Progression ◽

Ligand Expression

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Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy–treated immunologic nonresponders

Blood ◽

10.1182/blood-2011-01-329060 ◽

2011 ◽

Vol 118 (12) ◽

pp. 3263-3272 ◽

Cited By ~ 114

Author(s):

Stefania Piconi ◽

Serena Parisotto ◽

Giuliano Rizzardini ◽

Simone Passerini ◽

Roberta Terzi ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Antiretroviral Therapy ◽

Immune Activation ◽

Cd4 T Cells ◽

Immune Modulation ◽

T Regulatory Cells ◽

Plasmacytoid Dendritic Cells ◽

Therapy Interruption ◽

A Prospective Study

Abstract Despite optimal suppression of HIV replication, restoration of CD4+ T cells is not always achieved in antiretroviral therapy–treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4+ T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count < 200 cells/mL or CD4 increase < 5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14+ cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4+ (CD4+/Ki67+) and CD14+ (CD14+/CD69+) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4-expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFNα-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNFα production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4+ T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/2009-1-16-03-2009.

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