Volume 4.44 | Nov 16

Immune Regulation News 4.44 November 16, 2012
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Recognition of the Nonclassical Major Histocompatibility Complex Class I Molecule H2-M3 by the Receptor Ly49A Regulates the Licensing and Activation of NK Cells
The specific recognition of H2-M3 by Ly49A regulated the ‘licensing’ of natural killer (NK) cells and mediated ‘missing-self’ recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. [Nat Immunol]
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PUBLICATIONS (Ranked by impact factor of the journal)

Neutrophil Infiltration during Inflammation Is Regulated by PILRα via Modulation of Integrin Activation
Scientists found that paired immunoglobulin-like type 2 receptor alpha (PILRα), an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs, negatively regulated neutrophil infiltration during inflammation. [Nat Immunol] Abstract

Network Analysis Reveals Centrally Connected Genes and Pathways Involved in CD8+ T Cell Exhaustion versus Memory
These studies revealed differences between exhausted and memory CD8+ T cells including the following: lack of coordinated transcriptional modules of quiescence during exhaustion, centrally connected hub genes, pathways such as transcription factors, genes involved in regulation of immune responses, and DNA repair genes, as well as differential connectivity for genes including T-bet, Eomes, and other transcription factors. [Immunity] Abstract

IL-7 and IL-15 Instruct the Generation of Human Memory Stem T Cells from Naïve Precursors
Researchers showed that it is possible to differentiate in vitro, expand and gene modify in clinically compliant conditions CD8+ memory stem T cells lymphocytes starting from naïve precursors. Requirements for the generation of this T-cell subset, described as CD62L+CCR7+CD45RA+CD45R0+IL-7Rα+CD95+, are CD3/CD28 engagement and culture with IL-7 and IL-15. [Blood] Abstract

Tissue-Resident Memory CD8+ T Cells Continuously Patrol Skin Epithelia to Quickly Recognize Local Antigen
Investigators demonstrated that antigen-specific CD8+ T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. [Proc Natl Acad Sci USA] Abstract | Full Article

Interleukin 15 Provides Relief to Cytotoxic T Lymphocytes from Regulatory T Cell-Mediated Inhibition: Implications for Adoptive T-Cell Based Therapies of Lymphoma
As recombinant IL-15 is approaching clinical applications, investigators assessed the effects of this cytokine on the proliferation and antitumor activity of cytotoxic T lymphocytes in the presence of regulatory T cells. [Clin Cancer Res] Abstract

Preferential Depletion of Gut CD4-Expressing iNKT Cells Contributes to Systemic Immune Activation in HIV-1 Infection
Researchers examined key regulatory invariant receptor natural killer T (iNKT) cells in the gut, the largest reservoir of lymphocytes and a key arena of HIV-1 pathogenesis. Results suggested a potentially important contribution of gut iNKT-cell imbalance in determining the systemic immune activation that is the hallmark of HIV-1 pathogenesis. [Mucosal Immunol] Abstract

CD8+ T Cells Mediate RAS-Induced Psoriasis-Like Skin Inflammation through IFN-γ
Investigators expressed activated H-RASV12G in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses, and increased T helper type 1 (Th1)/Th17 and T cell type 1 (Tc1)/Tc17 skin infiltration. [J Invest Dermatol] Abstract

Potent Induction of Antibody-Secreting B Cells by Human Dermal-Derived CD14+ Dendritic Cells Triggered by Dual TLR Ligation
The authors showed that CD14+ dermal-derived dendritic cells (DDCs) express mRNA for TLRs 1-9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14+ DDCs, as shown by enhanced expression of B cell stimulatory cytokines and more pronounced phenotypic maturation. [J Immunol] Abstract

Regulatory T Cell Kinetics in the Peripheral Blood of Patients with Crohn’s Disease
Scientists demonstrated enhanced proliferation within the T regulatory cell population from patients with Crohn’s disease when compared to non-T regulatory cells and T regulatory cells from healthy control subjects. They speculated that T regulatory cells isolated from the periphery of patients with Crohn’s disease experience persistent antigen stimulation resulting in excess proliferative rates. [Hum Immunol] Abstract

Dissecting T Cell Contraction In Vivo Using a Genetically Encoded Reporter of Apoptosis
Researchers demonstrated that contraction is a widespread process occurring uniformly in all organs tested and targeting phenotypically diverse T cells. Importantly, they identified a critical window of time during which antigen encounters act to antagonize T cell apoptosis, supporting a causal link between antigen clearance and T cell contraction. [Cell Rep] Abstract

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REVIEWS
Recognition of CD1d-Restricted Antigens by Natural Killer T Cells
This review focuses on the defining features and emerging generalities regarding how natural killer T cells specifically recognize self, microbial and synthetic lipid-based antigens that are presented by CD1d. [Nat Rev Immunol] Abstract
INDUSTRY NEWS

Colby and MannKind Sign License and Joint Development Agreement to Develop and Commercialize Cancer Immunotherapy Products
Colby Pharmaceutical Company and MannKind Corporation announced a license agreement granting Colby exclusive worldwide rights to develop and commercialize disease-specific antigen compounds and intra-lymph node delivery technologies from MannKind’s novel MKC1106 active immunotherapy programs, which are currently being developed for the treatment of melanoma, prostate, hematological disorders and other human cancers. [MannKind Corporation] 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

NewLink Genetics Receives European Orphan Designation for Algenpantucel-L Immunotherapy to Treat Pancreatic Cancer
NewLink Genetics Corporation announced that the European Commission (EC) has designated HyperAcute-Pancreas® Immunotherapy (algenpantucel-L) as an orphan medicinal product under Regulation (EC) No. 141/2000 of the European Parliament and of the Council of 16 December 1999 on Orphan Medicinal Products. [NewLink Genetics Corporation] Press Release

Opexa Receives Clinical Trial Approval from Health Canada for Novel T-Cell Therapy
Opexa Therapeutics, Inc., a company developing Tcelna™, a novel T-cell therapy for multiple sclerosis, announced that Health Canada has approved the Company’s Clinical Trial Application. [Opexa Therapeutics, Inc.] Press Release

POLICY NEWS

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)

EVENTS
NEW Keystone Symposia on Molecular and Cellular Biology: Understanding Dendritic Cell Biology to Advance Disease Therapies
March 3-8, 2013
Keystone, United States

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

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 – 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)


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