Volume 5.23 | Jun 21

Immune Regulation News 5.23 June 21, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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Exploring the MHC-Peptide Matrix of Central Tolerance in the Human Thymus
Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes (MHCs) on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. To shed light on the so-far unknown human thymic peptide repertoire, researchers analyzed peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. [Nat Commun] Full Article

How Ex Vivo Models Drive Progress in HIV Research: Read the Research Profiles
PUBLICATIONS (Ranked by impact factor of the journal)

B7-H5 Costimulates Human T Cells via CD28H
Scientists describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. [Nat Commun] Abstract

Host Defense and Recruitment of Foxp3+ T Regulatory Cells to the Lungs in Chronic Mycobacterium tuberculosis Infection Requires Toll-Like Receptor 2
To directly link the reduced number of Foxp3+ T regulatory cells (Tregs) to the increased inflammation present in mice lacking Toll-like receptor 2 (TLR2KO), scientists used a macrophage adoptive transfer model. At seven weeks post-M. tuberculosis infection, TLR2KO mice, which were adoptively transferred with WT macrophages, displayed enhanced accumulation of Tregs in the lungs and a concomitant reduction in inflammation in contrast with control mice that received TLR2KO macrophages. [PLoS Pathog] Full Article

T Helper (TH)2 Cytokines from Malignant Cells Suppress TH1 Responses and Enforce a Global TH2 Bias in Leukemic Cutaneous T-Cell Lymphoma
The authors analyzed phenotype and cytokine production in malignant and benign leukemic cutaneous T-cell lymphoma (L-CTCL) T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL. [Clin Cancer Res] Abstract

AAV8 Induces Tolerance in Murine Muscle as a Result of Poor APC Transduction, T Cell Exhaustion and Minimal MHCI Upregulation on Target Cells
Following gene transfer of AAV2/8 to the muscle, C57BL/6 mice showed long-term expression of an nLacZ transgene with minimal immune activation. Scientists showed that pre-exposure to AAV2/8 can also induce tolerance to the more immunogenic AAV2/rh32.33 vector, preventing otherwise robust T-cell activation and allowing stable transgene expression. [Mol Ther] Abstract

Antiviral Vaccines License T Cell Responses by Suppressing Granzyme B Levels in Human Plasmacytoid Dendritic Cells
Researchers demonstrated that intrinsic granzyme B (GrB) production by plasmacytoid dendritic cells (pDC) is significantly inhibited in vitro and in vivo by clinically used vaccines against viral infections such as tick-borne encephalitis. They showed that pDC GrB levels inversely correlate with the proliferative response of coincubated T cells and that GrB suppression by a specific Ab or a GrB substrate inhibitor results in enhanced T cell proliferation, suggesting a predominant role of GrB in pDC-dependent T cell licensing. [J Immunol] Abstract

Chloroquine Treatment Enhances Regulatory T Cells and Reduces the Severity of Experimental Autoimmune Encephalomyelitis
Researchers assessed whether chloroquine (CQ) treatment alters the frequency of regulatory T cells and dendritic cells in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on experimental autoimmune encephalomyelitis, an experimental model for human multiple sclerosis, was investigated as well. [PLoS One] Full Article

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The Role of the Immune System in Governing Host-Microbe Interactions in the Intestine
To facilitate homeostasis, the immune system ensures that the diverse microbial load is tolerated and anatomically contained, while remaining responsive to microbial breaches and invasion. Although the microbiota is required for intestinal immune development, immune responses also regulate the structure and composition of the intestinal microbiota. The authors discuss recent advances in the understanding of these complex interactions and their implications for human health and disease. [Nat Immunol] Abstract

Dendritic Cells of the Oral Mucosa
An overview of the phenotype and distribution of dendritic cells (DCs) in the oral mucosa is provided. In addition, the role of the various oral DC subsets in inducing immunity vs. tolerance, as well as their involvement in several oral pathologies is discussed. [Mucosal Immunol] Abstract

Review Series on Immune Responses in Neurodegenerative Diseases: Innate and Adaptive Immune Responses in Neurodegeneration and Repair
While the idea of immune privilege was first discussed over 70 years ago by Sir Peter Medawar who was awarded the Nobel Prize with Sir Frank Macfarlane Burnet in 1960 for the discovery of acquired immune tolerance, it is clear that immune privilege is not absolute since immune reactions do, and indeed must take place to control infections in the central nervous system. [Immunology] Abstract

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Three Scientists to Receive Prestigious Novartis Prizes for Immunology at 15th International Congress of Immunology
The Novartis Prizes for Immunology are awarded to three scientists for their groundbreaking research into the biology of immune system T cells that advanced the prevention and treatment of a variety of diseases. [Novartis AG] Press Release

Lophius Wins $469K to Develop MS Diagnostic

Lophius Biosciences won €350,000 (about $469,000) over two years from Germany’s Federal Ministry of Education and Research to develop a blood-based diagnostic test, after joining Germany’s NEU2 academic-industry research consortium. Lophius’ T-Track® MS is designed to support initial diagnoses of multiple sclerosis (MS) and monitor MS disease progression. The diagnostic uses the company’s “Reverse T-Cell Technology” platform technology, which unlike current diagnostic methods exploits the maturation processes induced in antigen-presenting cells through interaction with activated T helper cells. [Genetic Engineering & Biotechnology News] Press Release

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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 LT3 – 3rd International Lymphoid Tissue Meeting
September 15-17, 2013
Rotterdam, Netherlands

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NEW Postdoctoral Scientists – Immune Cell Biology (Medical Research Council – National Institute for Medical Research)

Postdoctoral Fellowship – Immune Regulation by Extracellular Matrix Proteins (Johns Hopkins University – School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Immunological Modeling (Université catholique de Louvain (UCL))

Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

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