Volume 2.35 | Sep 16

Human Immunology News 2.35 September 16, 2014
Human Immunology News
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Genes and Immunity – T Lymphocyte Activation Integrates Immunologic and Genetic History
Scientists analyzed blood samples collected from 348 healthy volunteers representing African, Asian or European ancestry. After the researchers genotyped the samples and isolated CD4+ T cells, the T cells were activated in cell culture to model their response to antigens. [Press release from Harvard Medical School discussing online prepublication in Science] Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Immune Dysregulation in Human Subjects with Heterozygous Germline Mutations in CTLA4
Researchers identified germline heterozygous mutations in cytotoxic T lymphocyte antigen-4 (CTLA-4) in subjects from four unrelated families suffering from severe immune dysregulation. While Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3+ regulatory T cells, hyperactivation of effector T cells and lymphocytic infiltration of target organs. [Science] Abstract

Neutrophils Sense Microbe Size and Selectively Release Neutrophil Extracellular Traps in Response to Large Pathogens
Investigators found that neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens, such as Candida albicans hyphae and extracellular aggregates of Mycobacterium bovis, but not in response to small yeast or single bacteria. [Nat Immunol] Abstract | Press Release | Video

Targeted Activation of Human Vγ9Vδ2-T Cells Controls Epstein-Barr Virus-Induced B Cell Lymphoproliferative Disease
The authors show that aminobisphosphonate pamidronate-expanded human Vγ9Vδ2-T cells efficiently killed Epstein-Barr virus-transformed autologous lymphoblastoid B cell lines through γ/δ-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. [Cancer Cell] Abstract | Graphical Abstract

Exhaustion of Bacteria-Specific CD4 T Cells and Microbial Translocation in Common Variable Immunodeficiency Disorders
Researchers demonstrate that the CD4 T cell exhaustion and functional impairment observed in common variable immunodeficiency patients is associated with bacterial translocation and that intravenous immunoglobulin G treatment resolves bacterial translocation and restores CD4 T cell functions. [J Exp Med] Abstract | Press Release

Activation-Induced Necroptosis Contributes to B-Cell Lymphopenia in Active Systemic Lupus Erythematosus
The authors demonstrate that co-activation of toll-like receptor 7 and B-cell receptor pathways is a core event for the survival/dead states of B cells in systemic lupus erythematosus. [Cell Death Differ] Full Article

Peripheral and Local Human Papillomavirus 16-Specific CD8+ T-Cell Expansions Characterize Erosive Oral Lichen Planus
To investigate the molecular mechanisms underlying dysregulation of T-cell immune responses in patients with oral lichen planus (OLP), researchers studied the diversity and antigen-specificity of the T-cell receptor (TCR) expressed by CD8+ T-cells using dextramer staining, spectratyping and TCR sequencing in 10 OLP patients undergoing extracorporeal photochemotherapy. [J Invest Dermatol] Abstract

Human Thymus Medullary Epithelial Cells Promote Regulatory T-Cell Generation by Stimulating Interleukin-2 Production via ICOS Ligand
Using an exceptional panel of human thymic samples, scientists demonstrated that medullary thymus epithelial cells (mTECs) promote the generation of thymic T regulatory cells and favor their function. These effects were mediated through soluble factors and were mTEC specific since other cell types had no such effect. [Cell Death Dis] Full Article

Asthma Is Associated with Multiple Alterations in Anti-Viral Innate Signaling Pathways
Researchers compared the molecular pathway controlling type I interferon synthesis in human rhinovirus-stimulated peripheral blood mononuclear cells from asthmatic and healthy subjects. [PLoS One] Full Article

Angiotensin AT2 Receptor Stimulation Is Anti-Inflammatory in Lipopolysaccharide-Activated THP-1 Macrophages via Increased Interleukin-10 Production
The role of angiotensin AT2 receptor (AT2R) in the inflammatory activity of macrophages is not known. Scientists investigated whether AT2R activation stimulates an anti-inflammatory response in Toll-like receptor-4-induced inflammation. [Hypertens Res] Abstract

Increase in the Expression of CD4+CD25+ Lymphocytic T Cells in the Indeterminate Clinical Form of Human Chagas Disease after Stimulation with Recombinant Antigens of Trypanosoma cruzi
Scientists analyzed the levels of CD4+CD25+ T cells in chronic Chagas disease patients after in vitro stimulation of the peripheral blood mononuclear cells with cytoplasmic repetitive or flagellar repetitive T. cruzi antigens. [J Clin Immunol] Abstract

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Immune Modulation for Cancer Therapy
The authors review the preclinical and clinical development of ipilimumab. They outline the mode of action of these agents and other immune checkpoint inhibitors, the management of their toxicities, and how to adequately assess response to treatment. [Br J Cancer] Full Article

Visit our reviews page to see a complete list of reviews in the human immunology research field.
Inflammation May Be Key to Diabetes/Heart Disease Link
Inflammation may be the reason high blood sugar levels damage blood vessels, raising the possibility that anti-inflammatory medications might someday be used to lower the risk of blood vessel disease in people with diabetes. [Press release from the American Heart Association, Inc. discussing research presented at the American Heart Association’s High Blood Pressure Research Scientific Sessions 2014, San Francisco] Press Release

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Cancer Research UK, Cancer Research Technology and Asterias Biotherapeutics Partner to Trial Immunotherapy Vaccine for Lung Cancer
Cancer Research UK and Cancer Research Technology have reached an agreement with Asterias Biotherapeutics, Inc. to take forward Asterias’ novel immunotherapy treatment AST-VAC2 into clinical trials in subjects with non-small cell lung cancer. [Asterias Biotherapeutics, Inc.] Press Release

Fred Hutchinson Cancer Research Center and Seattle BioMed Team Up on Malaria Clinical Trials
Researchers at Fred Hutchinson Cancer Research Center and the Seattle Vaccine Trials Unit have begun a collaboration with Seattle BioMed and its Malaria Clinical Trials Center for upcoming malaria clinical research studies of experimental drugs that may prevent and/or treat malaria, which include a malaria challenge. [Fred Hutchinson Cancer Research Center] Press Release

MabVax Therapeutics Enters Agreements with Memorial Sloan Kettering Cancer Center and Juno Therapeutics for Development of Anti-Cancer Therapeutics
MabVax Therapeutics Holdings, Inc. announced it has entered into agreements with Memorial Sloan Kettering Cancer Center and Juno Therapeutics for the development of novel therapeutic products using antibody targeting sequences derived from the fully-human antibodies discovered using the company’s internally developed antibody discovery platform. [MabVax Therapeutics Holdings, Inc.] Press Release

Altor BioScience and Shenzhen Beike Biotechnology Announce License Agreement for Immunotherapeutic ALT-803 in China
Altor BioScience Corporation and Shenzhen Beike Biotechnology Co., Ltd. announced that they have entered into a license agreement to develop and commercialize ALT-803, Altor’s proprietary interleukin-15-based superagonist complex, in China. [Altor BioScience Corporation] Press Release

Merck KGaA Discontinues Clinical Development Program of Tecemotide as a Monotherapy in Stage III Non-Small Cell Lung Cancer
Merck KGaA announced that its biopharmaceutical division will discontinue the clinical development program of its investigational MUC1 antigen-specific cancer immunotherapy tecemotide as a monotherapy in Stage III non-small cell lung cancer. [Merck KGaA] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 3rd Conference of Translational Medicine on the Pathogenesis and Therapy of Immune-Mediated Disease
September 30-October 2, 2014
Milan, Italy

NEW 8th Vaccine & ISV Congress
October 26-28, 2014
Philadelphia, United States

Visit our events page to see a complete list of events in the human immunology community.
NEW Senior Research Fellow – Immunosenescence and Immune Exhaustion in Persistent Infections and Aging (Singapore Immunology Network A*STAR)

NEW Postdoctoral Fellow – Interleukin 23 in the Pathogenesis of Systemic Lupus Erythematosus (Beth Israel Medical Center)

Research Scientist – Immunology (Beijing Genomics Institute)

Postdoctoral Fellowship – Immunology (Huazhong University of Science and Technology)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064 )

Postdoctoral Position – Human Mucosal Immunology (INSERM)

Postdoctoral Fellow – Molecular Aspects of Autoimmunity (Singapore Immunology Network A*STAR)

Senior Manager – Inflammation, Fibrosis Biomarkers (Gilead Sciences)

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.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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