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Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation
- J. Immunol
, 2006
"... Type I IFN-producing cells (IPC) are sentinels of viral infections. Identification and functional characterization of these cells have been difficult because of their small numbers in blood and tissues and their complex cell surface phenotype. To overcome this problem in mice, mAbs recognizing IPC-s ..."
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Type I IFN-producing cells (IPC) are sentinels of viral infections. Identification and functional characterization of these cells have been difficult because of their small numbers in blood and tissues and their complex cell surface phenotype. To overcome this problem in mice, mAbs recognizing IPC-specific cell surface molecules have been generated. In this study, we report the identi-fication of new Abs specific for mouse IPC, which recognize the bone marrow stromal cell Ag 2 (BST2). Interestingly, previously reported IPC-specific Abs 120G8 and plasmacytoid dendritic cell Ag-1 also recognize BST2. BST2 is predominantly specific for mouse IPC in naive mice, but is up-regulated on most cell types following stimulation with type I IFNs and IFN-. The activation-induced promiscuous expression of BST2 described in this study has important implications for the use of anti-BST2 Abs in identification and depletion of IPC. Finally, we show that BST2 resides within an intracellular compartment corresponding to the Golgi apparatus, and may be involved in trafficking secreted cytokines in IPC. The Journal of Immunology, 2006, 177: 3260– 3265. T ype I IFN-producing cells (IPC),3 also called plasmacy-toid dendritic cells (DC), are early responders to viralinfections (1, 2). IPC detect viruses through TLRs 7 and 9 (3) and produce large amounts of type I IFN, i.e., IFN- and IFN- and proinflammatory chemokines. Through secretion of type I IFN, IPC direct both the innate and adaptive immune re-sponse by promoting NK cell and CD8 T cell cytotoxicity, en-hancing DC maturation, presenting Ag to T cells and inducing their Th1 polarization, and inducing B cell differentiation into Ab-secreting plasma cells (1, 2). IPC develop in the bone marrow and then circulate through the blood, eventually migrating into lym-phoid and nonlymphoid organs (1, 2), with increased recruitment into sites of inflammation (4, 5). Although IPC have significant effects on other cells, their numbers in blood and tissues are very small. This along with their complex surface phenotype makes them extremely difficult to identify. Specifically, mouse IPC are
Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen
, 2004
"... Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present ..."
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Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma. Key words: asthma • plasmacytoid dendritic cells • tolerance • mucosal immunity • regulatory T cell H.J. de Heer and H. Hammad contributed equally to this work. The online version of this article contains supplemental material.
Regulation of the type I IFN induction: a current view
- Int. Immunol
, 2005
"... The type I IFN-a/b gene family was identified about a quarter of a century ago as a prototype of many cytokine gene families, which led to the subsequent burst of studies on molecular mechanisms underlying cytokine gene expression and signaling. Although originally discovered for their activity to c ..."
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The type I IFN-a/b gene family was identified about a quarter of a century ago as a prototype of many cytokine gene families, which led to the subsequent burst of studies on molecular mechanisms underlying cytokine gene expression and signaling. Although originally discovered for their activity to confer an antiviral state on cells, more evidence has recently been emerging regarding IFN-a/b actions on cell growth, differentiation and many immunoregulatory activities, which are of even greater fundamental biological significance. Indeed, much attention has recently been focused on the induction and function of the IFN-a/b system regulated by Toll-like receptors (TLRs), which are critical for linking the innate and adaptive immunities. The understanding of the regulatory mechanisms of IFN-a/b gene induction by TLRs and viruses is an emerging theme, for which much new insight has been gained over the past few years.
Bovine plasmacytoid dendritic cells are the major source of type I interferon
"... Type I interferons (alpha/beta interferons [IFN-/]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in re ..."
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Type I interferons (alpha/beta interferons [IFN-/]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I IFN. These cells represented less than 0.1 % of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3 CD14 CD21 CD11c NK TCR CD4 MHC II CD45RB CD172a CD32). High levels of type I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and-mouth disease virus (FMDV) immune complexes. In contrast, immune complexes formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle. Foot-and-mouth disease virus (FMDV) is the etiological
REVIEW The Janus face of dendritic cells in cancer
"... On the basis of experimental models and some human data, we can assume that tumor outgrowth results from the balance between immunosurveillance (the extrinsic tumor suppressor mechanisms) and immunosubversion dictated by transformed cells and/or the corrupted surrounding microenvironment. Cancer imm ..."
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On the basis of experimental models and some human data, we can assume that tumor outgrowth results from the balance between immunosurveillance (the extrinsic tumor suppressor mechanisms) and immunosubversion dictated by transformed cells and/or the corrupted surrounding microenvironment. Cancer immunosurveil-lance relies mainly upon conventional lymphocytes exerting either lytic or secretory functions, whereas immunosubversion results from the activity of regulatory T or suppressor myeloid cells and soluble mediators. Although specific tools to target or ablate dendritic cells (DCs) became only recently available, accumulating evidence points to the critical role of the specialized DC system in dictating most of the conventional and regulatory functions of tumor-specific T lymphocytes. Although DC can be harnessed to silence tumor develop-ment, tumors in turn can exploit DC to evade immunity. Indeed, DCs harbor defects in their differentiation and stimulatory functions in cancer-bearing hosts and can actively promote T-cell tolerance to self-tumor antigens. In this review, we will focus on the dual role of DC during tumor progression and discuss pharmacoimmunological strategies to harness DC against cancer.
Dendritic cell differentiation and immune tolerance to insulin-related peptides in Igf2-deficient mice
- Journal of Immunology
, 2006
"... There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2/ mice. Phenotypically, some immunological parameters such as lymphoid ..."
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There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2/ mice. Phenotypically, some immunological parameters such as lymphoid organ morphology and cellularity were unaltered in Igf2/ mice, but an increase of CD8 cells and a decrease of B220 cells were observed in spleen. In vitro, the development of bone marrow-derived dendritic cells was affected by the absence of Igf2 expression. After maturation, a higher percentage of immature dendritic cells was observed in Igf2/ population, together with a secondary decrease in allogenic T cell proliferation. Activation of T cells was also affected by the lack of expression of this growth factor. The profile of B cell response in mutant mice immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 Abs that was absent in Igf2/ mice. The influence of IGF-2 upon tolerance to insulin was also assessed in this model, and this showed that IGF-2 also intervenes in tolerance to insulin. The presence of a T-dependent response in Igf2-deficient mice should allow cloning of specific “forbidden ” T CD4 lymphocytes directed against IGF-2, as well as further investigation of their possible pathogenic properties against insulin family. The Journal of Immunology, 2006, 176: 4651–4657. I nsulin-like growth factors 1 and 2 (IGF-1/2)3 are members ofthe insulin hormone family that exert a prominent role in fetaland postnatal development (1, 2). Null mutant mice for Igf1 show a marked growth deficiency with 60 % of normal body weight, a variable neonatal lethality frequency depending on ge-
Thesis Supervisor Signature redacted
, 2015
"... 2 Enhancement of HIV vaccine efficacy via lipid nanoparticle-based adjuvants by ..."
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2 Enhancement of HIV vaccine efficacy via lipid nanoparticle-based adjuvants by
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"... In presenting this thesis in partial fulfillment of the requirements for a Postgraduate degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying of this thesis in any manner, in ..."
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In presenting this thesis in partial fulfillment of the requirements for a Postgraduate degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying of this thesis in any manner, in whole or in part, for scholarly purposes may be granted by the professor or professors who supervised my thesis work or, in their absence, by the Head of the Department or the Dean of the College in which my thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Saskatchewan in any scholarly use which may be made of any material in my thesis.
IFN- γ upon IL-4 Stimulation
, 2013
"... This article cites 46 articles, 25 of which you can access for free at: ..."
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