Immune Regulation News Volume 4.45 | Nov 23 2012

The Tetraspanin CD37 Orchestrates the α₄ß₁ Integrin-Akt Signaling Axis and Supports Long-Lived Plasma Cell Survival
Researchers found that the four-transmembrane protein CD37 was essential for B cell survival and long-lived protective immunity. CD37-deficient mice had reduced numbers of immunoglobulin G-secreting plasma cells in lymphoid organs compared to those in wild-type mice, which the authors attributed to increased apoptosis of plasma cells in the germinal centers of the spleen, areas in which B cells proliferate and are selected. [Science] Abstract

NAADP Activates Two-Pore Channels on T Cell Cytolytic Granules to Stimulate Exocytosis and Killing
Researchers identified the Ca²⁺-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) and its recently identified molecular target, two-pore channels, as being important for T cell receptor signaling in cytotoxic T lymphocytes. [Curr Biol] Abstract

PLAU Inferred from a Correlation Network Is Critical for Suppressor Function of Regulatory T Cells
Several genes are known to be important for murine regulatory T cells (Tregs), but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. Researchers describe a strategy to identify the key genes directly from an undirected correlation network which they reconstructed from a very high time-resolution transcriptome during the activation of human Tregs/CD4⁺ T-effector cells. [Mol Syst Biol] Full Article

Endogenous IL-21 Regulates Pathogenic Mucosal CD4 T-Cell Responses during Enhanced RSV Disease in Mice
Researchers report that, in BALB/c mice infected with respiratory syncytial virus (RSV), interleukin-21 (IL-21) depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. [Mucosal Immunol] Full Article

A Converse 4-1BB and CD40 Ligand Expression Pattern Delineates Activated Regulatory T Cells (Treg) and Conventional T Cells Enabling Direct Isolation of Alloantigen-Reactive Natural Foxp3+ Treg 
Scientists demonstrated that activated natural Treg (nTreg) and activated conventional T cells differ in their 4-1BB and CD40 ligand (CD40L) expression signatures, allowing a clear dissection from each other. Based on the expression of 4-1BB and absence of CD40L expression, human alloantigen-reactive Foxp3⁺ nTreg can be directly isolated from MLR cultures with high purity. [J Immunol] Abstract

HCV-Infected Hepatocytes Drive CD4⁺CD25⁺Foxp3⁺ Regulatory T-Cell Development through the Tim-3/Gal-9 Pathway
To explore how Tim-3/Gal-9 interactions regulate hepatitis C virus (HCV)-mediated regulatory T (Treg) cell development, researchers provide pilot data showing that HCV-infected human hepatocytes express higher levels of Gal-9 and TGF-ß, and up-regulate Tim-3 expression and regulatory cytokines TGF-ß/IL-10 in co-cultured human CD4⁺ T cells, driving conventional CD4⁺ T cells into CD25⁺Foxp3⁺ Treg cells. [Eur J Immunol] Abstract

VEGF Directly Suppresses Activation of T Cells from Ascites Secondary to Ovarian Cancer via VEGF Receptor Type 2
Researchers found that the addition of vascular endothelial growth factor (VEGF) in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3⁺ T cells expressed VEGF receptor-2 on their surface upon activation. [Br J Cancer] Abstract

Frequency of CD4⁺FOXP3⁺ Regulatory T-Cells at Early Stages after HLA-Mismatched Allogeneic Hematopoietic SCT Predicts the Incidence of Acute GVHD
Scientists measured regulatory T-cells (Tregs) in peripheral blood as early as possible after HLA-mismatched allogeneic hematopoietic SCT (alloHSCT), and assessed the incidence of acute GVHD (aGVHD). Flow cytometric analyses revealed that at the second week after HSCT, patients with aGVHD had significantly lower Treg:CD4⁺T-cell ratios than those without aGVHD. [Bone Marrow Transplant] Abstract

CVID Patients with Autoimmunity Have Elevated T Cell Expression of Granzyme B and HLA-DR and Reduced Levels of Treg Cells
Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity. [J Clin Pathol] Abstract

Novartis Receives FDA Approval for Flucelvax^®, the First Cell-Culture Vaccine in US to Help Protect Against Seasonal Influenza
Novartis announced that the US Food and Drug Administration (FDA) approved the use of Flucelvax^® (Influenza Virus Vaccine), the first cell-culture-derived vaccine, for individuals 18 years of age and older. Flucelvax utilizes full-scale cell-culture manufacturing technology, an alternative production method to traditional egg-based production. [Novartis] Press Release

Grant Supports Gottschalk’s Osteosarcoma Immunotherapy Research
Research on using an immunotherapy approach to treating osteosarcoma by a Baylor College of Medicine pediatric oncologist is being supported by a $100,000 grant from the Cookies for Kids’ Cancer Foundation. [Baylor College of Medicine] Press Release

Stem Cell Pioneer Recognized for 20 Years of Discovery and Innovation
Dr. David Harris, Professor of Immunology at the University of Arizona and a scientific pioneer in the field of stem cell banking, was the recipient of the Arizona BioIndustry Association™ 2012 award for “20 Years of Discovery and Innovation”. [PR Newswire Association LLC] 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 Keystone Symposia: B Cell Development and Function
February 10-15, 2013
Keystone, United States

NEW Keystone Symposia: HIV Vaccines
February 10-15, 2013
Keystone, United States

NEW Keystone Symposia: Autophagy, Inflammation and Immunity
February 17-22, 2013
Montreal, Canada

Visit our events page to see a complete list of events in the immune regulation community.

Product Quality Scientist (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Quality Control Analyst (STEMCELL Technologies, Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Postdoctoral Fellow – Department of Microbiology and Immunology (Penn State University College of Medicine)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Postdoctoral Research Fellow (Singapore Immunology Network [A*STAR])

Research Associate in T Cell Immunology (Karolinska Institute, Department of Clinical Neuroscience)

Postdoctoral Position – Immunology (University of Helsinki, Institute of Biotechnology)

Researcher: Treg Cell Therapy for AID (Università Vita-Salute San Raffaele)

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