Human Immunology News Volume 2.44 | Nov 25 2014

The Immune Synapse Clears and Excludes Molecules above a Size Threshold
Natural killer cells assess target cell health via interactions at the immune synapse that facilitates signal integration and directed secretion. Quantitative fluorescence microscopy of nanometer-scale dextrans within synapses formed by various effector-target cell conjugates reveal that molecules are excluded in a size-dependent manner at activating synapses. [Nat Commun] Full Article | Press Release

Biallelic Loss-of-Function Mutation in ​NIK Causes a Primary Immunodeficiency with Multifaceted Aberrant Lymphoid Immunity
Investigators studied patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the ​MAP3K14 gene encoding ​NIK (NF-κB-inducing kinase). Loss of kinase activity of mutant ​NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF-κB signaling. [Nat Commun] Full Article

HIV-1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels
HIV-1 seroconverters from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow up. The frequency of activated T-cells was increased in HIV-1 infected Ugandans compared to community matched uninfected individuals, however did not differ significantly between viral subtypes. [J Infect Dis] Abstract

In Vivo Maintenance of Human Regulatory T Cells during CD25 Blockade
The authors investigated the effect of daclizumab-mediated CD25 blockade on regulatory T cell (Treg) homeostasis in patients with relapsing-remitting multiple sclerosis. They report that daclizumab therapy caused an ~50% decrease in Tregs over a 52-week period. [J Immunol] Abstract

The Effects of CCR5 Inhibition on Regulatory T-Cell Recruitment to Colorectal Cancer
Tumor-infiltrating lymphocytes were phenotyped for chemokine receptors using flow cytometry. Human colorectal cancer-regulatory T cells (Treg) were more proliferative and activated than other T cells suggesting that local proliferation could provide an alternative explanation for observed tumor Treg enrichment.
[Br J Cancer] Abstract

BST2/Tetherin Is Constitutively Expressed on Human Thymocytes with the Phenotype and Function of Treg Cells
BST2⁺ thymocytes express Foxp3 and CD25, consistent with the phenotype of natural regulatory T (Treg) cells, and exert suppressive activity as they impair the proliferation of autologous CD3⁺ thymocytes. [Eur J Immunol] Abstract

Human Natural Killer Cell MicroRNA: Differential Expression of MIR181A1B1 and MIR181A2B2 Genes Encoding Identical Mature MicroRNAs
Researchers tested the hypothesis that natural killer cells differentially transcribe the two genes during development and in response to immune regulatory cytokines. [Genes Immun] Abstract

Activation of the JAK/STAT Pathway in Behcet’s Disease
Using canonical pathway enrichment analysis, Janus family of kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was identified as activated in both CD14⁺ monocytes and in CD4⁺ lymphocytes in Behcet’s disease. [Genes Immun] Abstract

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Advances in Skin Grafting and Treatment of Cutaneous Wounds
The authors review the classic paradigms of wound healing and evaluate how recent discoveries have enriched our understanding of this process. They evaluate current and experimental approaches to treating cutaneous wounds, with an emphasis on cell-based therapies and skin transplantation. [Science] Abstract

Classical and Non-Classical MHC I Molecule Manipulation by Human Cytomegalovirus: So Many Targets – But How Many Arrows in the Quiver?
The authors summarize achievements from more than two decades of intense research on how human cytomegalovirus manipulates major histocompatibility complex class I (MHC I) molecules and escapes elimination by the immune system. [Cell Mol Immunol] Full Article

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George Tsokos, MD, Honored by Lupus Foundation and American College of Rheumatology
George Tsokos, MD, Chief of Rheumatology at Beth Israel Deaconess Medical Center and a national leader in the field of lupus research was honored by both the Lupus Foundation of America and the American College of Rheumatology (ACR) with two prestigious awards presented during the 2014 ACR Annual Scientific Meeting in Boston. [Beth Israel Deaconess Medical Center] Press Release

Health Canada Clears Immunovaccine to Conduct Phase II Clinical Trial of DPX-Survivac in Recurrent Lymphoma
Immunovaccine Inc. announced that it has received clearance from Health Canada to conduct a Phase II clinical study of DPX-Survivac in patients with diffuse large B cell lymphoma. [Immunovaccine Inc.] Press Release

Bristol-Myers Squibb and Five Prime Therapeutics Announce Exclusive Clinical Collaboration to Evaluate the Combination of Investigational Immunotherapies Opdivo (Nivolumab) and FPA008 in Six Tumor Types
Bristol-Myers Squibb Company and Five Prime Therapeutics, Inc. announced that they have entered into an exclusive clinical collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of combining Opdivo with FPA008, Five Prime’s monoclonal antibody that inhibits colony stimulating factor-1 receptor. [Bristol-Myers Squibb Company] Press Release

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Postdoctoral Scientist – Immunotherapy (Children’s Hospital of Eastern Ontario Research Institute)

Research Scientist – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

Research Technician – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Research Associate – Interleukin-17 Producing T Cells in Rheumatic Disease (King’s College London)

Postdoctoral Position – Tumor Immunology (Cancer Research Center of Lyon)

PhD Studentship – Role of Mucus on the Impact of Gut Bacteria on Health (University of East Anglia)

Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

PhD Studentship – Effects of Probiotics on Immunity in the Human Ageing Gut (University of East Anglia)

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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