Immune Regulation News Volume 6.48 | Dec 19 2014

Detection of Self-Reactive CD8⁺ T Cells with an Anergic Phenotype in Healthy Individuals
The authors show that regulatory T cells can render self-reactive human CD8⁺ T cells anergic in vitro, likely by controlling the costimulatory function of antigen-presenting cells. They detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. [Science] Abstract

Myeloid-Derived Suppressor Activity Is Mediated by Monocytic Lineages Maintained by Continuous Inhibition of Extrinsic and Intrinsic Death Pathways
Using genetic manipulation of cell death pathways, scientists found the monocytic suppressor-cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death. [Immunity] Abstract | Graphical Abstract | Press Release

The Coinhibitory Receptor CTLA-4 Controls B Cell Responses by Modulating T Follicular Helper, T Follicular Regulatory, and T Regulatory Cells
Researchers show deletion of CTLA-4 in adult mice increased Tfh and Tfr cell numbers and augmented B cell responses. In the effector phase, loss of CTLA-4 on Tfh cells resulted in heightened B cell responses, whereas loss of CTLA-4 on Tfr cells resulted in defective suppression of antigen-specific antibody responses. [Immunity] Full Article | Graphical Abstract

Essential Role for Autophagy during Invariant NKT Cell Development
Scientists report that, in mice with a conditional deletion of the essential autophagy gene Atg7 in the T-cell compartment, thymic invariant natural killer T (iNKT) cell development—unlike conventional T-cell development—is blocked at an early stage and mature iNKT cells are absent in peripheral lymphoid organs. [Proc Natl Acad Sci USA] Abstract | Full Article

PTPN2 Controls Differentiation of CD4⁺ T Cells and Limits Intestinal Inflammation and Intestinal Dysbiosis
Loss of protein tyrosine phosphatase non-receptor type 2 (PTPN2) in the T-cell compartment causes enhanced induction of T helper (Th)1 and Th17 cells, but impaired induction of regulatory T cells in several mouse colitis models. This results in increased susceptibility to intestinal inflammation and intestinal dysbiosis which is comparable with that observed in Crohn’s disease patients. [Mucosal Immunol] Abstract

Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions
Scientists demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a Toll-like receptor 4-dependent manner that results in enhanced survival to septic shock in mice. [Cell Rep] Full Article | Graphical Abstract

The Kinase Itk and the Adaptor TSAd Change the Specificity of the Kinase Lck in T Cells by Promoting the Phosphorylation of Tyr¹⁹²
Researchers found that a conserved tyrosine phosphorylation site (Tyr¹⁹²) within the Src homology 2 domain of Lck was required for proper T cell activation and formation of cell-cell conjugates between T cells and antigen-presenting cells. [Sci Signal] Abstract

HSP70 Mediates Degradation of the p65 Subunit of Nuclear Factor κB to Inhibit Inflammatory Signaling
Investigators found that the chaperone protein HSP70 (heat shock protein of 70 kD) was required for the PDLIM2-mediated degradation of p65 and suppression of nuclear factor κB signaling in lipopolysaccharide-treated dendritic cells. [Sci Signal] Abstract

Functional Expression Cloning Identifies COX-2 as a Suppressor of Antigen-Specific Cancer Immunity
Using functional expression cloning and T-cell receptor transgenic mice, scientists identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against the cytotoxicity induced by activated, antigen-specific T cells. [Cell Death Dis] Full Article

Leukotrienes Induce the Migration of Th17 Cells
Researchers show that Th17 cells express high levels of leukotriene B4 receptor 1 (LTB4R1) and cysteinyl leukotriene receptor 1 (CysLTR1). Th17 cells migrated under the guidance of leukotriene B4 and D4. The migration of Th17 cells was more efficient than that of Th1 and Th2 cells, and it was blocked by specific inhibitors of LTB4R1 or CysLTR1. [Immunol Cell Biol] Abstract

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Antiviral B Cell and T Cell Immunity in the Lungs
Well-timed, appropriately placed and tightly regulated T cell and B cell responses are essential for protection from infection and limitation of symptoms, whereas poorly regulated inflammation contributes to tissue damage and disease. Recent advances in understanding adaptive immunity should facilitate vaccine development and reduce the global effect of respiratory viruses. [Nat Immunol] Abstract

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ImmunoCellular Therapeutics Announces Issuance of Key Patent For ICT-107 Cancer Vaccine
ImmunoCellular Therapeutics, Ltd. announced that the US Patent and Trademark Office has issued a key patent covering ImmunoCellular’s product candidate ICT-107, a dendritic cell-based immunotherapeutic vaccine targeting six tumor antigens that are commonly expressed on glioblastoma. [ImmunoCellular Therapeutics, Ltd.] Press Release

Inovio Pharmaceuticals Initiates DNA Immunotherapy Trial for Breast, Lung and Pancreatic Cancers
Inovio Pharmaceuticals, Inc. announced it has initiated a Phase I trial of its hTERT DNA immunotherapy alone or in combination with Inovio’s IL-12 immune activator in adults with breast, lung, or pancreatic cancer at high risk of relapse after surgery and other cancer treatments. [Inovio Pharmaceuticals, Inc.] Press Release

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Postdoctoral Fellow – Tyrosine Phosphatase in Rheumatoid Arthritis (La Jolla Institute for Allergy & Immunology)

Postdoctoral Research Associate – Immunology (University of Edinburgh)

Postdoctoral Position – Immunology (Centre Léon Bérard)

Postdoctoral Position – Mucosal Immunology (Karolinska Institute)

Research Associate – B Cell Biology (King’s College London)

Researcher – Antitumor Immune Cell Response (ACAVI)

Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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