Immune Regulation News Volume 5.14 | Apr 19 2013

miR-17~92 Regulates Effector and Memory CD8 T-Cell Fates by Modulating Proliferation in Response to Infections
Researchers showed a dynamic regulation of microRNAs (miRs) as CD8 T-cells differentiate from naïve to effector and memory states, with short-lived effectors transiently expressing higher levels of oncogenic miR-17~92 compared to the relatively less proliferating memory-fated effectors. [Blood] Abstract

Murine Natural Killer Cell Licensing and Regulation by T Regulatory Cells in Viral Responses
Investigators showed in vivo confirmation of the physiologic effects of licensing with differential effects of natural killer subsets on anti-murine cytomegalovirus responses after syngeneic hematopoietic stem cell transplantation or regulatory T-cell depletion. [Proc Natl Acad Sci USA] Abstract

Mutually Exclusive Regulation of T Cell Survival by Interleukin-7R and Antigen Receptor-Induced Signals
Scientists showed that T cell receptor ligation actively inhibits homeostatic survival signals while initiating a new, dominant survival program. This switch is mediated by a change in the expression of pro- and anti-apoptosis proteins through the downregulation of Bcl-2 and the induction of Bim, A1 and Bcl-xL. Results identify a molecular switch that can serve as an attractive target for inducing antigen-specific tolerance in treating autoimmune disease patients and transplant recipients. [Nat Commun] Full Article

Butyrophilin Btn2a2 Inhibits TCR Activation and Phosphatidylinositol 3-Kinase/Akt Pathway Signaling and Induces Foxp3 Expression in T Lymphocytes
The butyrophilin-related protein Btn2a2 was upregulated on murine APC including CD19⁺ B cells, CD11b⁺F4/80⁺ peritoneal macrophages, and CD11c⁺ bone marrow-derived dendritic cells after activation with LPS or Pam3CysK4, suggesting a role in modulation of T lymphocytes. [J Immunol] Abstract

Chemokine Receptor CXCR6-Dependent Hepatic NK T Cell Accumulation Promotes Inflammation and Liver Fibrosis
Researchers hypothesized that chemokine receptor CXCR6 and its ligand CXCL16 control NKT cell migration and functionality in liver fibrosis. In patients with chronic liver diseases, CXCR6 and CXCL16 expression was intrahepatically upregulated compared with controls. In murine liver, Cxcl16 was strongly expressed by endothelium and macrophages, whereas lymphocyte populations expressed CXCR6. [J Immunol] Abstract

Communication between Human Mast Cells and CD4⁺ T Cells through Antigen-Dependent Interactions
To study the T cell-stimulatory potential of human mast cells, CD34⁺ stem cell-derived mast cells were generated. These cells expressed HLA-DR when stimulated with IFN-γ, and, importantly, presented peptide and protein for activation of antigen-specific CD4⁺ T cells. [Eur J Immunol] Abstract

Galectin-3 Negatively Regulates the Frequency and Function of CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells and Influences the Course of Leishmania major Infection
The authors found, in a model of Leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral regulatory T (T_REG) cells both in draining lymph nodes and sites of infection. Galectin-3-deficient T_REG cells displayed higher CD103 expression, showed greater suppressive capacity and synthesized higher amounts of interleukin-10 compared with their wild-type counterpart. [Eur J Immunol] Abstract

The Kindlin 3 PH Domain Has an Essential Role in Integrin LFA-1-Mediated B Cell Adhesion and Migration
To gain understanding of how kindlin 3 controls leukocyte function, researchers focused on its PH domain and find that deletion of this domain eliminates the ability of kindlin 3 to participate in adhesion and migration of B cells mediated by the leukocyte integrin LFA-1. [J Biol Chem] Abstract | Full Article

Functional Impairment of Microglia Coincides with Beta-Amyloid Deposition in Mice with Alzheimer-Like Pathology
To uncover and characterize putative changes in the functionality of microglia during Alzheimer’s disease, scientists directly assessed microglial behavior in two mouse models of Alzheimer’s disease. Using in vivo two-photon microscopy and acute brain slice preparations, they found that important microglial functions – directed process motility and phagocytic activity – were strongly impaired in mice with Alzheimer’s disease-like pathology compared to age-matched non-transgenic animals. [PLoS One] Full Article | Press Release

The Integration of T Cell Migration, Differentiation and Function
The authors review classic and emerging concepts, highlight the challenge of integrating new observations with existing T cell classification schemes and summarize the heuristic framework provided by viewing T cell differentiation and function first through the prism of migration. [Nat Rev Immunol] Abstract

Molecular Mechanisms of Natural Killer Cell Activation in Response to Cellular Stress
This review provides a brief introduction to natural killer (NK) cells and the relevant receptors and ligands involved in direct responses to cellular stress. This will be followed by an in-depth discussion surrounding the various intrinsic responses to stress that can naturally engage NK cells, and how therapeutic agents may induce specific activation of NK cells and other innate immune cells by activating cellular responses to stress. [Cell Death Differ] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.

Immunomedics Develops T-Cell Redirecting Bispecific Antibodies as Potential Therapeutics for Solid and Liquid Tumors
Immunomedics, Inc. announced the development of novel T-cell redirecting agents made as DOCK-AND-LOCK™ complexes by tethering a single-chain variable fragment that binds to CD3 on T cells to different antibody fragments that target tumor antigens. A study on the mechanism of action of epratuzumab was also presented. [Press release from Immunomedics, Inc. discussing research presented at the 2013 Annual Meeting of the American Association for Cancer Research (AACR), Washington] Press Release

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NW Bio’s Phase III Trial with DCVax®-L for Brain Cancer “Adopted” as a National Priority Trial in UK
Northwest Biotherapeutics (NW Bio), a biotechnology company developing DCVax^® personalized immune therapies for solid tumor cancers, announced that the Company’s Phase III clinical trial for glioblastoma multiforme brain cancer has been “adopted” as a national priority trial in the UK, under the “adoption” program managed by the National Institute for Health Research, which is part of the UK’s National Health System. [Northwest Biotherapeutics, Inc.] Press Release

Prima Biomed Awarded Japanese Patent for CVac
Prima BioMed Ltd announced that it has been granted a patent from the Japanese Patent Office that protects methods used in the manufacture of CVac. The method of use claims secured in patent number 5192020 entitled “Use of mannose receptor-bearing antigen presenting cells for the manufacture of medicament for eliciting cytotoxic T cell response to antigen” provide for the treatment of patients with dendritic cells that have been pulsed with mannan fusion protein conjugated to an antigen, including but not limited to mucin 1. [Prima BioMed Ltd] Press Release

The First Patient Treated Using Celsense MRI Cell Tracking Technology
Celsense, Inc. announced that the first patient to have transplanted cells imaged by magnetic resonance imaging (MRI) using the company’s Cell Sense technology has been treated at the University of Pittsburgh Cancer Institute. The Phase I clinical trial was cleared by the US FDA for the purposes of developing information regarding cell migration following administration of live cells. This application, involving the use of an autologous dendritic cell vaccine to treat colorectal cancer, is the first time the trafficking of a live cell cancer vaccine in patients has been visualized by MRI in the United States. [Celsense, Inc.] Press Release

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Therapeutic Goods Administration (Australia)

NEW 15^th International Congress of Immunology (ICI)
August 22-27, 2013
Milan, Italy

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

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

PhD Studentship – Mucosal immunology (KU Leuven Translational Research Center for Gastrointestinal Disorders)

PhD Candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – Immunology (Institut Pasteur)

Postdoctoral Position – Immunology (INSERM 1020)

Postdoctoral Fellow – Immunotherapeutics in Childhood Cancer (Perelman School of Medicine at the University of Pennsylvania)

Postdoctoral Position – Type 1 Diabetes and Systemic Lupus Erythematosus (University of Florida)

PhD Studentship – Thymic Dendritic Cells and Regulation of T-Cell Development (University of Birmingham / MRC Centre for Immune Regulation)

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