In Vivo Induction of Type 1-Like Regulatory T Cells Using Genetically Modified B Cells Confers Long-Term IL-10-Dependent Antigen-Specific Unresponsiveness

Ahangarani, Roxana Roohi; Janssens, Wim; VanderElst, Luc; Carlier, Vincent; VandenDriessche, Thierry; Chuah, Marinee; Weynand, Birgit; Vanoirbeek, Jeroen; Jacquemin, Marc; Saint-Remy, Jean-Marie

doi:10.4049/jimmunol.0901777

Cited by 39 publications

(31 citation statements)

References 52 publications

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“…DCs secreting IL-10 and/or TGF-b 1 are known to generate Tr1 and Th3 T-regulatory cells that inhibit T cells by secretion of IL-10 or TGF-b, respectively (Mills, 2004;Qadura et al, 2008). In addition, Tr1 regulatory cells are able to suppress antibody responses toward allergens and protect mice from allergic asthma (Ahangarani et al, 2009). Consistent with this, we observed reduced frequencies of the effector T cell population in the peripheral blood and splenocytes of mice that received cytokine-conditioned DCs when compared with mice that received DCs only.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice

et al. 2012

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“…A number of studies suggest that IL-10-producing B cells are important for the generation and/or maintenance of the regulatory T cell (T REG ) pool [46,63-72]. However, a recent study [73] and our previously published data [23] do not support this view.…”

Section: B10 Cell Regulatory Effectsmentioning

confidence: 93%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

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“…Experiments that induced overexpression of the type 1 diabetes-associated autoantigens GAD65 or insulin specifically in B lymphocytes resulted in immune tolerance that was attributed to an increase in Treg cell differentiation (117). Similarly, retroviral transduction of B cells with a construct containing the allergen DerP2 followed by adoptive transfer of the transduced B cells into allergen-sensitized mice resulted in immune tolerance and expansion of a subset of Tregs (118). A series of studies using B cells that were not genetically modified in a mixed lymphocyte reaction demonstrated that both CD4 + and CD8 + alloantigen-specific…”

Section: B-cell Interactions With Regulatory T-cell Populationsmentioning

confidence: 99%

Multiple Mechanisms of Immune Suppression by B Lymphocytes

Klinker

Lundy

2011

Mol Med

110

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Suppression of the immune system after the resolution of infection or inflammation is an important process that limits immunemediated pathogenesis and autoimmunity. Several mechanisms of immune suppression have received a great deal of attention in the past three decades. These include mechanisms related to suppressive cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-β, produced by regulatory cells, and mechanisms related to apoptosis mediated by death ligands, Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), expressed by killer or cytotoxic cells. Despite many lines of evidence supporting an important role for B lymphocytes as both regulatory and killer cells in many inflammatory settings, relatively little attention has been given to understanding the biology of these cells, their relative importance or their usefulness as therapeutic targets. This review is intended to give an overview of the major mechanisms of immunosuppression used by B lymphocytes during both normal and inflammatory contexts. The more recent discoveries of expression of granzyme B, programmed death 1 ligand 2 (PD-L2) and regulatory antibody production by B cells as well as the interactions of regulatory and killer B cells with regulatory T cells, natural killer T (NKT) cells and other cell populations are discussed. In addition, new evidence on the basis of independent characterizations of regulatory and killer CD5 + B cells point toward the concept of a multipotent suppressor B cell with seemingly high therapeutic potential.

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In Vivo Induction of Type 1-Like Regulatory T Cells Using Genetically Modified B Cells Confers Long-Term IL-10-Dependent Antigen-Specific Unresponsiveness

Cited by 39 publications

References 52 publications

Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice

Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Multiple Mechanisms of Immune Suppression by B Lymphocytes

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