Journal of Immunology
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Comment on "TLR9-Dependent Activation of Dendritic Cells by DNA from Leishmania major Favors Th1 Cell Development and the Resolution of Lesions"
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PMID: 19923471 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 20, 2009 Category: Allergy & Immunology Authors: Bogdan C, Schleicher U Tags: J Immunol Source Type: journals
A Crucial Door to the Mast Cell Mystery Knocked In.Email this article to a colleague.
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PMID: 19923472 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 20, 2009 Category: Allergy & Immunology Authors: Kawakami T Tags: J Immunol Source Type: journals
Pillars Article: Fate of Bone Marrow-Derived Cultured Mast Cells After Intracutaneous, Intraperitoneal, And Intravenous Transfer Into Genetically Mast Cell-Deficient W/Wv Mice. Evidence That Cultured Mast Cells Can Give Rise To Both Connective Tissue Type And Mucosal Mast Cells. The Journal of Experimental Medicine. 1985. 162: 1025-1043.Email this article to a colleague.
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PMID: 19923473 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 20, 2009 Category: Allergy & Immunology Authors: Nakano T, Sonoda T, Hayashi C, Yamatodani A, Kanayama Y, Yamamura TI, Asai H, Yonezawa T, Kitamura Y, Galli SJ Tags: J Immunol Source Type: journals
What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?Email this article to a colleague.
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The route of vaccination is important in influencing immune responses at the initial site of pathogen invasion where protection is most effective. Immune responses required for mucosal protection can differ vastly depending on the individual pathogen. For some mucosal pathogens, including acute self-limiting infections, high-titer neutralizing Abs that enter tissue parenchyma or transude into the mucosal lumen are sufficient for clearing cell-free virus. However, for pathogens causing chronic infections such as HIV, hepatitis C virus, herpes viruses, mycobacteria, and fungal and parasitic infections, a single arm of th...
Source: Journal of Immunology - November 20, 2009 Category: Allergy & Immunology Authors: Belyakov IM, Ahlers JD Tags: J Immunol Source Type: journals
Activated CD8+ T-Effector/Memory Cells Eliminate CD4+ CD25+ Foxp3+ T-Suppressor Cells from Tumors via FasL Mediated Apoptosis.Email this article to a colleague.
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Tumor-resident CD8(+) T cells display a quiescent effector/memory phenotype that is maintained in part by infiltrating CD4(+) CD25(+) Foxp3(+) T-suppressor cells. Intratumoral delivery of IL-12, in contrast, can restore cytotoxic function to tumor-associated CD8(+) T cells and induce the apoptotic death of T-suppressor cells. Depletion of CD8(+) T cells from tumors before IL-12 treatment resulted in the abrogation of treatment-mediated T-suppressor cell apoptosis revealing a link between CD8(+) T cell activation and T-suppressor elimination. Furthermore, IL-12 failed to induce T-suppressor cell loss in IFN-gamma- or Fa...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Kilinc MO, Rowswell-Turner RB, Gu T, Virtuoso LP, Egilmez NK Tags: J Immunol Source Type: journals
Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis.Email this article to a colleague.
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In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-gamma. Cell-based therapy...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Zhang Q, Shi S, Liu Y, Uyanne J, Shi Y, Shi S, Le AD Tags: J Immunol Source Type: journals
Langerin+CD8{alpha}+ Dendritic Cells Are Critical for Cross-Priming and IL-12 Production in Response to Systemic Antigens.Email this article to a colleague.
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Distinct dendritic cell (DC) subsets differ with respect to pathways of Ag uptake and intracellular routing to MHC class I or MHC class II molecules. Murine studies suggest a specialized role for CD8alpha(+) DC in cross-presentation, where exogenous Ags are presented on MHC class I molecules to CD8(+) T cells, while CD8alpha(-) DC are more likely to present extracellular Ags on MHC class II molecules to CD4(+) T cells. As a proportion of CD8alpha(+) DC have been shown to express langerin (CD207), we investigated the role of langerin(+)CD8alpha(+) DC in presenting Ag and priming T cell responses to soluble Ags. When spl...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Farrand KJ, Dickgreber N, Stoitzner P, Ronchese F, Petersen TR, Hermans IF Tags: J Immunol Source Type: journals
IL-7 Enhances Thymic Human T Cell Development in "Human Immune System" Rag2-/-IL-2R{gamma}c-/- Mice without Affecting Peripheral T Cell Homeostasis.Email this article to a colleague.
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IL-7 is a central cytokine in the development of hematopoietic cells, although interspecies discrepancies have been reported. By coculturing human postnatal thymus hematopoietic progenitors and OP9-huDL1 stromal cells, we found that murine IL-7 is approximately 100-fold less potent than human IL-7 for supporting human T cell development in vitro. We investigated the role of human IL-7 in newborn BALB/c Rag2(-/-)gamma(c)(-/-) mice transplanted with human hematopoietic stem cells (HSC) as an in vivo model of human hematopoiesis using three approaches to improve IL-7 signaling: administration of human IL-7, ectopic expres...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, Maijoor KA, Weijer K, Cornelissen JJ, Blom B, Di Santo JP, Spits H, Legrand N Tags: J Immunol Source Type: journals
Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption.Email this article to a colleague.
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The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast differentiation. Chemokines are known to regulate cell migration and adhesion. CX3CL1 (also called fractalkine) is a unique membrane-bound chemokine that has dual functions for cells expressing its receptor CX3CR1: a potent chemotactic factor in its soluble form and a type of efficient cell adhesion molecule in its membrane-bound form. In this paper, we demonstrate a novel role of CX3CL1 in osteoblast-induced osteoclast differentiation. We found that osteoclast precursors selectively expressed C...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Koizumi K, Saitoh Y, Minami T, Takeno N, Tsuneyama K, Miyahara T, Nakayama T, Sakurai H, Takano Y, Nishimura M, Imai T, Yoshie O, Saiki I Tags: J Immunol Source Type: journals
Enhanced Susceptibility to Leishmania Infection in Resistant Mice in the Absence of Immediate Early Response Gene X-1.Email this article to a colleague.
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Immediate early response gene X-1 (IEX-1) is a stress-inducible gene abundantly expressed in macrophages and T cells following various stimuli. To explore a potential role for IEX-1 in control of the susceptibility to Leishmania major infection, the inflammatory response during cutaneous leishmaniasis was evaluated in 129Sv/C57BL/6-resistant mice in the presence or absence of IEX-1. Null mutation of IEX-1 enhanced the susceptibility of the mice to L. major infection, and aggravated inflammatory responses in comparison with wild-type control mice. The excessive inflammation was not ascribed to a Th2-biased immune respon...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Akilov OE, Ustyugova IV, Zhi L, Hasan T, Wu MX Tags: J Immunol Source Type: journals
Distinct Antiviral Roles for Human 2',5'-Oligoadenylate Synthetase Family Members against Dengue Virus Infection.Email this article to a colleague.
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In this study, we determined the role of the human OAS/RNase L pathway in host defense against dengue virus (DEN) infection and assessed the antiviral potential of each isoform in the human OAS family. DEN replication was reduced by overexpression and enhanced by knockdown of RNase L expression, indicating a protective role for RNase L against DEN replication in human cells. The human OAS1 p42, OAS1 p46, and OAS3 p100, but not the other OAS isoforms, blocked DEN replication via an RNase L-dependent mechanism. Furthermore, the anti-DEN activities of these three OAS isoforms correlated with their ability to trigger RNase L a...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL Tags: J Immunol Source Type: journals
Infection with Arginase-Deficient Leishmania major Reveals a Parasite Number-Dependent and Cytokine-Independent Regulation of Host Cellular Arginase Activity and Disease Pathogenesis.Email this article to a colleague.
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In this study, we compared the infectivity and impact on host cellular immune response in vitro and in vivo of wild-type (WT) L. major with that of a parasite arginase null mutant (arg(-)) L. major. We found that arg(-) L. major are impaired in their macrophage infectivity in vitro independent of host inducible NO synthase activities. As with in vitro results, the proliferation of arg(-) L. major in animal infections was also significantly impaired in vivo, resulting in delayed onset of lesion development, attenuated pathology, and low parasite burden. Despite this attenuated pathology, the production of cytokines by cells...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Muleme HM, Reguera RM, Berard A, Azinwi R, Jia P, Okwor IB, Beverley S, Uzonna JE Tags: J Immunol Source Type: journals
Cutting Edge: Inhibitory Effects of CD4 and CD8 on T Cell Activation Induced by High-Affinity, Noncognate Ligands.Email this article to a colleague.
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It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand cross-reactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (K(D)=17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings s...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Chervin AS, Stone JD, Bowerman NA, Kranz DM Tags: J Immunol Source Type: journals
Autoimmune Regulator Deficiency Results in Decreased Expression of CCR4 and CCR7 Ligands and in Delayed Migration of CD4+ Thymocytes.Email this article to a colleague.
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In conclusion, Aire regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes. These results suggest a novel mechanism behind the Aire-dependent induction of central tolerance.
PMID: 19923453 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Laan M, Kisand K, Kont V, Möll K, Tserel L, Scott HS, Peterson P Tags: J Immunol Source Type: journals
CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice.Email this article to a colleague.
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Peribronchial lymphoid follicles have recently been identified as one of the hallmark features of (severe) chronic obstructive pulmonary disease (COPD). However, little is known about the relative contribution of peribronchial lymphoid follicles vs mediastinal lymph nodes in inflammatory responses in COPD patients and animal models. In a murine model of COPD, we studied inflammatory responses in airways, lungs, and mediastinal lymph nodes of wild-type (WT) vs CCR7 knockout (CCR7(-/-)) mice upon subacute or chronic exposure to cigarette smoke (CS). Although crucial for the organization of the secondary lymphoid organs, ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Demoor T, Bracke KR, Vermaelen KY, Dupont L, Joos GF, Brusselle GG Tags: J Immunol Source Type: journals
Matrix Metalloproteinase (MMP)-1 and MMP-3 Induce Macrophage MMP-9: Evidence for the Role of TNF-{alpha} and Cyclooxygenase-2.Email this article to a colleague.
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Matrix metalloproteinase (MMP)-9 (gelatinase B) participates in a variety of diverse physiologic and pathologic processes. We recently characterized a cyclooxygenase-2 (COX-2)-->PGE(2)-->EP4 receptor axis that regulates macrophage MMP-9 expression. In the present studies, we determined whether MMPs, commonly found in inflamed and neoplastic tissues, regulate this prostanoid-EP receptor axis leading to enhanced MMP-9 expression. Results demonstrate that exposure of murine peritoneal macrophages and RAW264.7 macrophages to MMP-1 (collagenase-1) or MMP-3 (stromelysin-1) lead to a marked increase in COX-2 expression,...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Steenport M, Khan KM, Du B, Barnhard SE, Dannenberg AJ, Falcone DJ Tags: J Immunol Source Type: journals
An Innate Response to Allogeneic Nonself Mediated by Monocytes.Email this article to a colleague.
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The mammalian innate immune system has evolved diverse strategies to distinguish self from microbial nonself. How the innate immune system distinguishes self-tissues from those of other members of the same species (allogeneic nonself) is less clear. To address this question, we studied the cutaneous hypersensitivity response of lymphocyte-deficient RAG(-/-) mice to spleen cells transplanted from either allogeneic or syngeneic RAG(-/-) donors. We found that RAG(-/-) mice mount a specific response to allogeneic cells characterized by swelling and infiltration of the skin with host monocytes/macrophages and neutrophils. T...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Zecher D, van Rooijen N, Rothstein DM, Shlomchik WD, Lakkis FG Tags: J Immunol Source Type: journals
CD69 Controls the Pathogenesis of Allergic Airway Inflammation.Email this article to a colleague.
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Airway inflammation and airway hyperresponsiveness are central issues in the pathogenesis of asthma. CD69 is a membrane molecule transiently expressed on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. In CD69-deficient mice, OVA-induced eosinophilic airway inflammation, mucus hyperproduction, and airway hyperresponsiveness were attenuated. Cell transfer of Ag-primed wild-type but not CD69-deficient CD4 T cells restored the induction of allergic inflammation in CD69-deficient mice, indicating a critical role of C...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Miki-Hosokawa T, Hasegawa A, Iwamura C, Shinoda K, Tofukuji S, Watanabe Y, Hosokawa H, Motohashi S, Hashimoto K, Shirai M, Yamashita M, Nakayama T Tags: J Immunol Source Type: journals
Cutting Edge: Normal Regional Lymph Node Enrichment of Antigen-Specific Regulatory T Cells with Autoimmune Disease-Suppressive Capacity.Email this article to a colleague.
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In this study, we quantified disease-specific Treg (DS-Treg) as Treg that preferentially suppress one autoimmune disease over another in day 3 thymectomized recipients. A striking difference was found among individual lymph nodes (LN) of normal mice; Treg from draining LN were 15-50 times more efficient than those of nondraining LN at suppressing autoimmune diseases of ovary, prostate, and lacrimal glands. The difference disappeared upon auto-Ag ablation and returned upon auto-Ag re-expression. In contrast, the CD4(+)CD25(-) effector T cells from different individual LN induced multiorgan inflammation with comparable organ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Wheeler KM, Samy ET, Tung KS Tags: J Immunol Source Type: journals
Soluble B and T Lymphocyte Attenuator Possesses Antitumor Effects and Facilitates Heat Shock Protein 70 Vaccine-Triggered Antitumor Immunity against a Murine TC-1 Cervical Cancer Model In Vivo.Email this article to a colleague.
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B and T lymphocyte attenuator (BTLA)-herpesvirus entry mediator (HVEM) signaling coinhibitory pathway is believed to impair antitumor immune competences. An intriguing unresolved question is whether blockade of BTLA-HVEM guides an effective therapeutic tool against established tumors. To address this issue, we constructed a eukaryotic expression plasmid (psBTLA) that expressed the extracellular domain of murine BTLA (soluble form of BTLA), which could bind HVEM, the ligand of BTLA, and block BTLA-HVEM interactions. The data in this study showed that treatment by injection of psBTLA resulted in down-regulation of IL-10 ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Han L, Wang W, Fang Y, Feng Z, Liao S, Li W, Li Y, Li C, Maitituoheti M, Dong H, Lai Z, Gao Q, Xi L, Wu M, Wang D, Zhou J, Meng L, Wang S, Ma D Tags: J Immunol Source Type: journals
Viruses within the Flaviviridae Decrease CD4 Expression and Inhibit HIV Replication in Human CD4+ Cells.Email this article to a colleague.
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Viral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. Two flaviviruses are associated with a reduction in HIV replication or improved survival in HIV-infected people (dengue virus (DV) and GB virus type C (GBV-C)). GBV-C infection and expression of the GBV-C nonstructural protein 5A (NS5A) and the DV NS5 protein in CD4(+) T cells inhibit HIV replication in vitro. To determine whether the inhibitory effect on HIV replication is conserved among other flaviviruses and to characterize mechanism(s) of HIV inhibition, the ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Xiang J, McLinden JH, Rydze RA, Chang Q, Kaufman TM, Klinzman D, Stapleton JT Tags: J Immunol Source Type: journals
Signaling Crosstalk during Sequential TLR4 and TLR9 Activation Amplifies the Inflammatory Response of Mouse Macrophages.Email this article to a colleague.
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The TLR family of pattern recognition receptors is largely responsible for meditating the activation of macrophages by pathogens. Because macrophages may encounter multiple TLR ligands during an infection, signaling crosstalk between TLR pathways is likely to be important for the tailoring of inflammatory reactions to pathogens. Here, we show that rather than inducing tolerance, LPS pretreatment primed the inflammatory response (e.g., TNF production) of mouse bone marrow-derived macrophages (BMM) to the TLR9 ligand, CpG DNA. The priming effects of LPS, which correlated with enhanced Erk1/2, JNK, and p38 MAPK activation...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: De Nardo D, De Nardo CM, Nguyen T, Hamilton JA, Scholz GM Tags: J Immunol Source Type: journals
IFN-{gamma} Expressed by T Cells Regulates the Persistence of Antigen Presentation by Limiting the Survival of Dendritic Cells.Email this article to a colleague.
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In this report we evaluated the mechanism of this curtailment. Ag presentation declined precipitously as the T cell response developed, and Ag presentation was not curtailed in mice that were deficient in CD8(+) T cells or MHC class II, suggesting that T cells regulate Ag presentation. Curtailment of Ag presentation was reduced in IFN-gamma-deficient mice, but not in mice with a deficiency/mutation in inducible NOS2, perforin, or Fas ligand. In hosts with no T cells (Rag1(-/-)), Ag presentation was not curtailed during the chronic stage of infection. However, adoptive transfer of wild-type, but not IFN-gamma(-/-), CD4(+) a...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Russell MS, Dudani R, Krishnan L, Sad S Tags: J Immunol Source Type: journals
New Design of MHC Class II Tetramers to Accommodate Fundamental Principles of Antigen Presentation.Email this article to a colleague.
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Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examine...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Landais E, Romagnoli PA, Corper AL, Shires J, Altman J, Wilson IA, Garcia KC, Teyton L Tags: J Immunol Source Type: journals
IL-23 Is Required for Protection against Systemic Infection with Listeria monocytogenes.Email this article to a colleague.
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Listeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Meeks KD, Sieve AN, Kolls JK, Ghilardi N, Berg RE Tags: J Immunol Source Type: journals
The Tpl2 Mutation Sluggish Impairs Type I IFN Production and Increases Susceptibility to Group B Streptococcal Disease.Email this article to a colleague.
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Sluggish was identified in a population of third generation mice descended from N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes exhibited impaired TNF-alpha production in response to all TLR ligands tested and displayed impaired type I IFN production in response to TLR7 and TLR9 stimulations. The phenotype was confined to a critical region on mouse chromosome 18 and then ascribed to a T to A transversion in the acceptor splice site of intron 4 at position 13346 of the Map3k8 gene, resulting in defective splicing. The Map3k8(Sluggish) mutation does not result in susceptibility to viral infections, ...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Xiao N, Eidenschenk C, Krebs P, Brandl K, Blasius AL, Xia Y, Khovananth K, Smart NG, Beutler B Tags: J Immunol Source Type: journals
Brain-Derived Neurotrophic Factor (BDNF) Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia.Email this article to a colleague.
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In this study, we observed that BDNF induced a sustained increase in [Ca(2+)]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosin-related kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca(2+)]i elevation. Pretreatment with BDNF significantly suppressed the rele...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Mizoguchi Y, Monji A, Kato T, Seki Y, Gotoh L, Horikawa H, Suzuki SO, Iwaki T, Yonaha M, Hashioka S, Kanba S Tags: J Immunol Source Type: journals
Cutting Edge: Depletion of Foxp3+ Cells Leads to Induction of Autoimmunity by Specific Ablation of Regulatory T Cells in Genetically Targeted Mice1.Email this article to a colleague.
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We have recently described two independent mouse models in which the administration of diphtheria toxin (DT) leads to specific depletion of regulatory T cells (Tregs) due to expression of DT receptor-enhanced GFP under the control of the Foxp3 promoter. Both mouse models develop severe autoimmune disorders when Foxp3(+) Tregs are depleted. Those findings were challenged in a recent study published in this journal suggesting the expression of Foxp3 in epithelial cells as the cause for disease development. By using genetic, cellular, and immunohistochemical approaches, we do not find evidence for Foxp3-expression in nonh...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Kim J, Lahl K, Hori S, Loddenkemper C, Chaudhry A, Deroos P, Rudensky A, Sparwasser T Tags: J Immunol Source Type: journals
Integration of Distinct Intracellular Signaling Pathways at Distal Regulatory Elements Directs T-bet Expression in Human CD4+ T Cells.Email this article to a colleague.
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In this study, we defined regulatory elements at the human T-bet locus and determined how signals originating at the TCR and at cytokine receptors are integrated to induce chromatin modifications and expression of this gene during human Th1 cell differentiation. We found that T cell activation induced two strong DNase I-hypersensitive sites (HS) and rapid histone acetylation at these elements in CD4(+) T cells. Histone acetylation and T-bet expression were strongly inhibited by cyclosporine A, and we detected binding of NF-AT to a HS in vivo. IL-12 and IFN-gamma signaling alone were not sufficient to induce T-bet expressio...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Placek K, Gasparian S, Coffre M, Maiella S, Sechet E, Bianchi E, Rogge L Tags: J Immunol Source Type: journals
Duality of Enhancer Functioning Mode Revealed in a Reduced TCR{beta} Gene Enhancer Knockin Mouse Model.Email this article to a colleague.
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The TCRbeta gene enhancer (Ebeta) commands TCRbeta gene expression through the lifespan of T lymphocytes. Genetic and molecular studies have implied that in early thymocytes, Ebeta directs chromatin opening over the Dbeta-Jbeta-Cbeta domains and triggers initial Dbeta-Jbeta recombination. In mature T cells, Ebeta is required for expression of the assembled TCRbeta gene. Whether these separate activities rely on distinct Ebeta regulatory sequences and involve differing modes of activation is unclear. Using gene targeting in mouse embryonic stem cells, we replaced Ebeta by a conserved core fragment (Ebeta169). We found t...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Bonnet M, Huang F, Benoukraf T, Cabaud O, Verthuy C, Boucher A, Jaeger S, Ferrier P, Spicuglia S Tags: J Immunol Source Type: journals
Neutrophils and Macrophages Cooperate in Host Resistance against Leishmania braziliensis Infection.Email this article to a colleague.
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Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of inf...
Source: Journal of Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Novais FO, Santiago RC, Báfica A, Khouri R, Afonso L, Borges VM, Brodskyn C, Barral-Netto M, Barral A, de Oliveira CI Tags: J Immunol Source Type: journals
0022-1767; +53873 new citationsEmail this article to a colleague.
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Source: Journal of Immunology - November 16, 2009 Category: Allergy & Immunology Tags: Report Source Type: journals
Comment on "Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation".Email this article to a colleague.
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PMID: 19890062 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Mabalirajan U, Agrawal A, Ghosh B Tags: J Immunol Source Type: journals
Comment on "Reduced cytotoxic function of effector CD8+ T cells is responsible for indoleamine 2,3-dioxygenase-dependent immune suppression".Email this article to a colleague.
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PMID: 19890063 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Sørensen RB, thor Straten P, Andersen MH Tags: J Immunol Source Type: journals
Immunostimulatory RNA oligonucleotides induce an effective antitumoral NK cell response through the TLR7.Email this article to a colleague.
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In this study, we show for the first time that immunostimulatory RNA oligonucleotides induce a NK cell response that prevents growth of NK-sensitive tumors. Treatment of mice with immunostimulatory RNA oligonucleotides activates NK cells in a sequence-dependent manner, leading to enhanced IFN-gamma production and increased cytotoxicity. Use of gene-deficient mice showed that NK activation is entirely TLR7-dependent. We further demonstrate that NK activation is indirectly induced through IL-12 and type I IFN production by dendritic cells. Reconstitution of TLR7-deficient mice with wild-type dendritic cells restores NK activ...
Source: Journal of Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Bourquin C, Schmidt L, Lanz AL, Storch B, Wurzenberger C, Anz D, Sandholzer N, Mocikat R, Berger M, Poeck H, Hartmann G, Hornung V, Endres S Tags: J Immunol Source Type: journals
HMGB1 enhances the proinflammatory activity of lipopolysaccharide by promoting the phosphorylation of MAPK p38 through receptor for advanced glycation end products.Email this article to a colleague.
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High mobility group box-1 (HMGB1) protein was originally characterized as a nuclear DNA-binding protein, and was described to have an extracellular role when involved in cellular activation and proinflammatory responses. In the present study, we have found that the proinflammatory activity of recombinant HMGB1 proteins is determined by the containing endotoxin level, and HMGB1 that contains few endotoxins fails to stimulate macrophages to secrete proinflammatory cytokines. HMGB1 acts as a ligand of receptor for advanced glycation end products (RAGE) and works in synergy with LPS in activating the macrophages in vitro. ...
Source: Journal of Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Qin YH, Dai SM, Tang GS, Zhang J, Ren D, Wang ZW, Shen Q Tags: J Immunol Source Type: journals
FoxP3+ regulatory T cells restrain splenic extramedullary myelopoiesis via suppression of hemopoietic cytokine-producing T cells.Email this article to a colleague.
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Extramedullary myelopoiesis occurs in peripheral organs such as spleen and produces many types of myeloid cells with diverse functions in response to inflammation and infection. It is increased during immune responses and chronic inflammation and is a significant factor in regulating inflammatory diseases and immunity. Increased myeloid cells are found in FoxP3-deficient mice but the mechanism has been unclear. We investigated the mechanism by which FoxP3(+) regulatory T cells regulate the extramedullary myelopoiesis. We found that Ab or genetic depletion of FoxP3(+) regulatory T cells greatly increased the number of t...
Source: Journal of Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Lee JH, Wang C, Kim CH Tags: J Immunol Source Type: journals
Increased Inflammation, Impaired Bacterial Clearance, and Metabolic Disruption after Gram-Negative Sepsis in Mkp-1-Deficient Mice.Email this article to a colleague.
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MAPKs are crucial for TNF-alpha and IL-6 production by innate immune cells in response to TLR ligands. MAPK phosphatase 1 (Mkp-1) deactivates p38 and JNK, abrogating the inflammatory response. We have previously demonstrated that Mkp-1(-/-) mice exhibit exacerbated inflammatory cytokine production and increased mortality in response to challenge with LPS and heat-killed Staphylococcus aureus. However, the function of Mkp-1 in host defense during live Gram-negative bacterial infection remains unclear. We challenged Mkp-1(+/+) and Mkp-1(-/-) mice with live Escherichia coli i.v. to examine the effects of Mkp-1 deficiency ...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Frazier WJ, Wang X, Wancket LM, Li XA, Meng X, Nelin LD, Cato AC, Liu Y Tags: J Immunol Source Type: journals
The DC-SIGN of Zebrafish: Insights into the Existence of a CD209 Homologue in a Lower Vertebrate and Its Involvement in Adaptive Immunity.Email this article to a colleague.
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Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN/CD209) has become hot topic in recent studies because of its important roles in immune responses and immune escape. CD209 has been well characterized in humans and several other mammals, but little documentation exists about it in lower vertebrates. This is the first report on the identification and functional characterization of a fish DC-SIGN/CD209 molecule. The zebrafish DC-SIGN/CD209 cDNA translates into 343 aa organized into three domains structurally conserved among vertebrates. An EPN motif essential for interacting with Ca(2+) and for recognizing mann...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Lin AF, Xiang LX, Wang QL, Dong WR, Gong YF, Shao JZ Tags: J Immunol Source Type: journals
Estrogen Regulates Transcription Factors STAT-1 and NF-{kappa}B to Promote Inducible Nitric Oxide Synthase and Inflammatory Responses.Email this article to a colleague.
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In this study, we report that activation of both STAT-1 and NF-kappaB signaling is essential for Con A-induced inducible NO synthase (iNOS) and NO in murine splenocytes. Estrogen enhances STAT-1 DNA-binding activity without increasing the expression of phosphorylated and total STAT-1 protein. We have recently reported that estrogen blocks the nuclear expression of NF-kappaB p65 and modifies nuclear NF-kappaBp50. Here, we demonstrated that both nuclear STAT-1 and NF-kappaB are modified by serine protease-mediated proteolysis, which resulted in altered STAT-1 and NF-kappaB activity/signaling in splenocytes from estrogen-trea...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Dai R, Phillips RA, Karpuzoglu E, Khan D, Ahmed SA Tags: J Immunol Source Type: journals
Coexistence of Closed and Open Conformations of Complement Factor B in the Alternative Pathway C3bB(Mg2+) Proconvertase.Email this article to a colleague.
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In this study, we have used single-particle electron microscopy and image processing to examine the C3bB(Mg(2+)) proconvertase. We describe two C3bB(Mg(2+)) conformations, one resembling cobra venom factor, likely representing the loading state of fB to C3b, and another identical with C3bB(Ni(2+)). These data illustrate the coexistence of C3b-bound fB in closed and open conformations that either exist in equilibrium or represent structural transitions during the assembly of the C3bB proconvertase.
PMID: 19890040 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Torreira E, Tortajada A, Montes T, Rodríguez de Córdoba S, Llorca O Tags: J Immunol Source Type: journals
Ineffective Vaccination against Solid Tumors Can Be Enhanced by Hematopoietic Cell Transplantation.Email this article to a colleague.
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In conclusion, these findings show that otherwise ineffective vaccination to solid nonhematologic tumors can be dramatically enhanced by HCT.
PMID: 19890041 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Filatenkov A, Müller AM, Tseng WW, Dejbakhsh-Jones S, Winer D, Luong R, Shizuru JA, Engleman EG, Strober S Tags: J Immunol Source Type: journals
Natural Occurring IL-17 Producing T Cells Regulate the Initial Phase of Neutrophil Mediated Airway Responses.Email this article to a colleague.
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In this study, we report that the immune system contains a unique set of natural occurring IL-17 producing cell, "natural" Th17 (nTh17), which are a memory-like T cell subset. The nTh17 cells can develop in the absence of the IL-6/STAT3 signaling axis required by inducible Th17 cells. The nTh17 cell population is distinct from conventional inducible Th17 cells, since nTh17 cells express substantial amounts of IL-17A (IL-17), but not IL-17F, under the control of the master regulator, RORgammat. The nTh17 cells simultaneously produce IFN-gamma. DO11.10 transgenic mice with a Rag(-/-) background (DO11.10 Rag(-/-)) lack nTh17 ...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Tanaka S, Yoshimoto T, Naka T, Nakae S, Iwakura YI, Cua D, Kubo M Tags: J Immunol Source Type: journals
Female and Male Sex Hormones Differentially Regulate Expression of Ifi202, an Interferon-Inducible Lupus Susceptibility Gene within the Nba2 Interval.Email this article to a colleague.
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Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F(1) male mice with the female sex hormone 17beta-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced e...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Panchanathan R, Shen H, Gubbels Bupp M, Gould KA, Choubey D Tags: J Immunol Source Type: journals
Sex Steroid Ablation Enhances Hematopoietic Recovery following Cytotoxic Antineoplastic Therapy in Aged Mice.Email this article to a colleague.
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In this study we have examined the effects of sex steroid ablation (SSA) on the recovery of lymphopoiesis in the bone marrow (BM) and thymus following treatment with the chemotherapeutic agent cyclophosphamide (Cy) in middle-aged and old mice. Furthermore, we have also examined the impact of this regeneration on peripheral immunity. SSA enhanced the recovery of BM resident hematopoietic stem cells and lymphoid progenitors and promoted lymphopoiesis. Interestingly, Cy alone caused a profound increase in the recently described common lymphoid progenitor 2 (CLP-2) population in the BM. In the thymus, SSA caused a profound inc...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Dudakov JA, Goldberg GL, Reiseger JJ, Vlahos K, Chidgey AP, Boyd RL Tags: J Immunol Source Type: journals
Cutting Edge: Memory CD8 T Cell Compartment Grows in Size with Immunological Experience but Nevertheless Can Lose Function.Email this article to a colleague.
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The size of the adaptive immune system is considered to be kept constant by the attrition of pre-existing memory. However, recently it was shown that the CD8 memory compartment can grow in size and the number of pre-existing memory is largely preserved, predicting that pre-existing immunity should be maintained (Vezys et al.; Nature 457: 196-199). Experimental proof for this assumption is still lacking. We address this question in the Listeria monocytogenes (L.m.) infection model and confirm the growth of size of the memory compartment by subsequent vaccination with modified vaccinia virus Ankara. We also find only mod...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Huster KM, Stemberger C, Gasteiger G, Kastenmüller W, Drexler I, Busch DH Tags: J Immunol Source Type: journals
Role of Double-Stranded RNA Pattern Recognition Receptors in Rhinovirus-Induced Airway Epithelial Cell Responses.Email this article to a colleague.
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Rhinovirus (RV), a ssRNA virus of the picornavirus family, is a major cause of the common cold as well as asthma and chronic obstructive pulmonary disease exacerbations. Viral dsRNA produced during replication may be recognized by the host pattern recognition receptors TLR-3, retinoic acid-inducible gene (RIG)-I, and melanoma differentiation-associated gene (MDA)-5. No study has yet identified the receptor required for sensing RV dsRNA. To examine this, BEAS-2B human bronchial epithelial cells were infected with intact RV-1B or replication-deficient UV-irradiated virus, and IFN and IFN-stimulated gene expression was de...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Wang Q, Nagarkar DR, Bowman ER, Schneider D, Gosangi B, Lei J, Zhao Y, McHenry CL, Burgens RV, Miller DJ, Sajjan U, Hershenson MB Tags: J Immunol Source Type: journals
NOD2 Ligation Subverts IFN-{alpha} Production by Liver Plasmacytoid Dendritic Cells and Inhibits Their T Cell Allostimulatory Activity via B7-H1 Up-Regulation.Email this article to a colleague.
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The nucleotide-binding oligomerization domain (NOD)2/CARD15 protein, which senses muramyl dipeptide (MDP), a product of bacterial peptidoglycan, appears to play an important role in regulating intestinal immunity. Although the liver is exposed to gut-derived MDP, the influence of NOD2 ligation on hepatic APC, in particular dendritic cells (DC), is unknown. Freshly isolated mouse liver and spleen plasmacytoid (p)DC expressed higher levels of NOD2 message than conventional myeloid (m)DC. Following MDP stimulation in vivo, liver pDC, but not mDC, up-regulated expression of IFN regulatory factor 4 (IRF-4), a negative regul...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Castellaneta A, Sumpter TL, Chen L, Tokita D, Thomson AW Tags: J Immunol Source Type: journals
Identification of Lipoteichoic Acid as a Ligand for Draper in the Phagocytosis of Staphylococcus aureus by Drosophila Hemocytes.Email this article to a colleague.
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Phagocytosis is central to cellular immunity against bacterial infections. As in mammals, both opsonin-dependent and -independent mechanisms of phagocytosis seemingly exist in Drosophila. Although candidate Drosophila receptors for phagocytosis have been reported, how they recognize bacteria, either directly or indirectly, remains to be elucidated. We searched for the Staphylococcus aureus genes required for phagocytosis by Drosophila hemocytes in a screening of mutant strains with defects in the structure of the cell wall. The genes identified included ltaS, which encodes an enzyme responsible for the synthesis of lip...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Hashimoto Y, Tabuchi Y, Sakurai K, Kutsuna M, Kurokawa K, Awasaki T, Sekimizu K, Nakanishi Y, Shiratsuchi A Tags: J Immunol Source Type: journals
Limited Role of CD4+Foxp3+ Regulatory T Cells in the Control of Experimental Cerebral Malaria.Email this article to a colleague.
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Cerebral malaria (CM) associated with Plasmodium berghei ANKA (PbA) infection is an accepted model of human CM. CM during PbA infection critically depends on sequestration of T cells into the brain. Several studies aimed to address the role of regulatory T cells (T(reg)) in modulating this pathogenic T cell response. However, these studies are principally hampered due to the fact that until recently no reagents were available to deplete Foxp3(+) T(reg) specifically. To study the function of T(reg) in the genesis of CM, we used depletion of T(reg) mice that are transgenic for a bacterial artificial chromosome expressing...
Source: Journal of Immunology - November 4, 2009 Category: Allergy & Immunology Authors: Steeg C, Adler G, Sparwasser T, Fleischer B, Jacobs T Tags: J Immunol Source Type: journals
