Immune Regulation News Volume 4.42 | Nov 2 2012

Mechanistic and Structural Insight into the Functional Dichotomy between IL-2 and IL-15
Consistent with their identical interleukin (IL)-2Rβ-γ_c dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Rα versus IL-15Rα determined cellular responsiveness. [Nat Immunol] Abstract

The Short Isoform of the CEACAM1 Receptor in Intestinal T Cells Regulates Mucosal Immunity and Homeostasis via Tfh Cell Induction
Previous studies on peripheral T cells show that carcinoembryonic antigen cell adhesion molecule like I (CEACAM1)-long (L) cytoplasmic tail isoforms predominate with little to no detectable CEACAM1-short (S) cytoplasmic tail isoforms in mouse and human. Researchers showed here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues, which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse. [Immunity] Abstract | Graphical Abstract

Dendritic Cells Tolerized with Adenosine A_2AR Agonist Attenuate Acute Kidney Injury
Researchers found that ex vivo adenosine 2A receptor (A_2AR)-induced tolerized DCs suppress NKT cell activation in vivo and provide a unique and potent cell-based strategy to attenuate organ ischemia/reperfusion injury. [J Clin Invest] Full Article | Press Release

Viral MHC Class I Inhibition Evades CD8⁺ T-Cell Effector Responses In Vivo but Not CD8⁺ T-Cell Priming
The authors found no major effect of MHC class I down-regulation on priming of functional cowpox virus-specific CD8⁺ T cells. Instead, they demonstrated that, during acute infection in vivo, MHC class I down-regulation prevents primed virus-specific CD8⁺ T cells from recognizing infected cells and exerting effector responses to control the infection. [Proc Natl Acad Sci USA] Abstract

C1q Limits Dendritic Cell Differentiation and Activation by Engaging LAIR-1
Functional analyses showed that C1q-mediated inhibition of monocyte-dendritic cell (DC) differentiation and C1q-mediated inhibition of IFN-α production by plasmacytoid DCs were both reversed by leukocyte-associated Ig-like receptor 2 (LAIR-2). Moreover, C1q-mediated inhibition of DC differentiation was reversed by LAIR-1 siRNA. Thus, C1q is a functional ligand for LAIR-1 restricting immune cell differentiation and activation. [Proc Natl Acad Sci USA] Abstract

Vaccination with Antigen-Transfected, NKT Cell Ligand-Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells
The authors established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the NKT immune cell receptor CD1d, loaded with the CD1d ligand alpha-galactosylceramide and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVCs activated invariant NKT cells elicited antigen-specific T cell responses with no adverse events. [Cancer Res] Abstract

Migrating Lymph Dendritic Cells Contain Intracellular CD40 that Is Mobilized to the Immunological Synapse during Interactions with Antigen-Specific T Lymphocytes
Researchers concluded that migrating lymph dendritic cells contain stores of CD40 that can be mobilized rapidly to the sites of interaction with Ag-specific T cells. The disappearance of CD40 by 24 hours may help in the regulation of T cell activation. [J Immunol] Abstract

IFN-γ Limits Th9-Mediated Autoimmune Inflammation through Dendritic Cell Modulation of IL-27
Investigators showed that IFN-γ inhibits Th9 differentiation both in vitro and in vivo. This suppressive activity was dependent on the transcription factor STAT-1. In addition to its direct inhibitory effect on Th9 differentiation, IFN-γ suppressed Th9 cells through the induction of IL-27 from dendritic cells. [J Immunol] Abstract

Dendritic Cell Central Nervous System Recruitment Correlates with Disease Severity in Experimental Autoimmune Encephalomyelitis via CCL2 Chemotaxis at the Blood-Brain Barrier through Paracellular Transmigration and ERK Activation
To further characterize the direct effect of chemokine ligand 2 (CCL2) in dendritic cell trafficking at the blood-brain barrier (BBB), researchers utilized an in vitro BBB model consisting of human brain microvascular endothelial cells to compare migratory patterns of monocyte-derived dendritic cells, CD4+ and CD8+ T cells. [J Neuroinflammation] Abstract | Full Article

The Activity of γδ T Cells against Pediatric Liver Tumor Cells and Spheroids in Cell Culture
Researchers aimed to specifically analyze the ability of ex vivo expanded γδ T cells to recognize and lyse hepatoblastoma and hepatocellular carcinoma cell lines in coculture assays. [Liver Int] Abstract

Advaxis Updates Phase II Cervical Cancer Trial Data
Advaxis, Inc. updated preliminary data from an ongoing randomized 110 patient Phase II trial of ADXS-HPV being conducted in India in women with recurrent/refractory cervical cancer who have failed previous cytotoxic therapy. [Press release from Advaxis, Inc. discussing research presented at the Society for Immunotherapy of Cancer (SITC) 27th Annual Meeting, North Bethesda] Press Release

Cellectis Presents Breakthrough in Fight against Cancer
Cellectis has announced successfully programming cells from the immune system (T cells) to kill cancer cells. [Press release from Cellectis discussing research presented at the European Society of Gene & Cell Therapy (ESGCT), Versailles] Press Release

Immune System Fighters Speak in Patterns of Proteins, Prefer Squishy Partners
When talking to the key immune system fighters known as T-cells, it helps to speak their language. Now researchers from Columbia University in New York and the University of Pennsylvania in Philadelphia have discovered two new conditions for communication that may help scientists one day harness the power of T-cells to fight diseases such as cancer. [Press release from EurekAlert! discussing research presented at the AVS 59th International Symposium and Exhibition, Tampa] Press Release

Wibi+Works, LLC Awarded $400,000
Wibi+Works, LLC has been awarded a $400,000 Phase I Small Business Innovation Research Grant from the National Institutes of Health. The grant will be used to fund the development of its adult allogeneic mesenchymal stem cell-based therapy for the anti-inflammatory treatment of rheumatoid arthritis. [Wibi+Works, LLC] Press Release

Compugen Announces Discovery of Two Novel Immune Checkpoint Targets for Cancer Immunotherapy
Compugen Ltd. announced the discovery and initial validation of two new drug target candidates for monoclonal antibody cancer therapy. In recent in vitro studies, both of these immune checkpoint molecules have shown distinct activity inhibiting two key subtypes of immune cells, natural killer cells and T cells. [Business Wire] 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)

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Product Manager – Hematopoietic (STEMCELL Technologies, Inc.)

Product Quality Scientist (STEMCELL Technologies, Inc.)

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

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

Postdoctoral Position – Immunology (San Raffaele Scientific Institute)

Research Associate – Quality Assurance (University of California)

Postdoctoral & PhD Student Positions – NK Cell-Based Anti-Cancer Immunotherapies (Medical University of Vienna)

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

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

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