Immune Regulation News Volume 6.04 | Feb 7 2014

Intrinsic CD4⁺ T Cell Sensitivity and Response to a Pathogen Are Set and Sustained by Avidity for Thymic and Peripheral Complexes of Self Peptide and MHC
Specific and nonspecific stimulation of LLO56 and LLO118 T cells, which transgenically express a T cell antigen receptor (TCR) specific for the same Listeria monocytogenes epitope, elicited distinct interleukin 2 and phosphorylated kinase Erk responses, the strength of which was set in the thymus and maintained in the periphery in proportion to the avidity of the binding of the TCR to the self peptide-major histocompatibility complex (MHC) complex. [Nat Immunol] Abstract

2B4 (CD244) Induced by Selective CD28 Blockade Functionally Regulates Allograft-Specific CD8⁺ T Cell Responses
Investigators identified a critical role for the co-inhibitory SLAM family member 2B4 in attenuating primary antigen-specific CD8⁺ T cell responses in the presence of immune modulation with selective CD28 blockade. [J Exp Med] Abstract

Mouse Model of Intrauterine Inflammation: Sex-Specific Differences in Long-Term Neurologic and Immune Sequelae
Researchers aimed to elucidate long-term (into adolescence and adulthood) neurological outcomes by assessing neurobehavioral development, MRI, immunohistochemistry and flow cytometry of cells of immune origin and to determine whether there are any sex-specific differences in brain development associated with intrauterine inflammation. They observed chronic brain inflammation in the offspring, with persistence of microglial activation and increased numbers of macrophages in the brain, ultimately resulting in neuronal loss. [Brain Behav Immun] Abstract | Press Release

Lymphatic Specific Disruption in the Fine Structure of Heparan Sulfate Inhibits Dendritic Cell Traffic and Functional T Cell Responses in the Lymph Node
Investigators demonstrated that genetically altering the fine structure (N-sulfation) of heparan sulfate specifically in mouse lymphatic endothelium significantly reduces dendritic cell trafficking to regional lymph nodes (LNs) in vivo. Moreover, this alteration had the unique functional consequence of reducing CD8⁺ T cell proliferative responses in draining LNs in an ovalbumin immunization model. [J Immunol] Abstract

IL-21 Promotes CD4 T Cell Responses by Phosphatidylinositol 3-Kinase-Dependent Upregulation of CD86 on B Cells
Researchers identified a novel role for IL-21 as an inducer of the costimulatory ligand CD86 on B lymphocytes. CD86 provides critical signals through T cell-expressed CD28 that promote T cell activation in response to Ag engagement. [J Immunol] Abstract

Plasmacytoid Dendritic Cells License Regulatory T Cells, Upon iNKT-Cell Stimulation, to Prevent Autoimmune Diabetes
Findings revealed that upon repetitive invariant (i)NKT cell stimulation, plasmacytoid dendritic cells are critical for the recruitment of Treg cells in the pancreatic islets and the prevention of type 1 diabetes development. [Eur J Immunol] Abstract

CD40 Signaling Drives B Lymphocytes Into an Intermediate Memory-Like State, Poised between Naïve and Plasma Cells
Data revealed that CD40 signaling mediated BLIMP1 down regulation occurs by non-Pax5/non-Bcl6 dependent mechanisms, indicating novel mechanisms at work that add to the complexity of understanding of B cell master regulatory molecules like BLIMP1 and Pax5. [J Cell Physiol] Abstract

Generation and Characterization of Regulatory Dendritic Cells Derived from Murine Induced Pluripotent Stem Cells
Scientists attempted to generate and characterize regulatory dendritic cells (DCregs) from murine induced pluripotent stem (iPS) cells. The generated iPS-DCregs demonstrated high CD11b/c and low CD40, CD80, CD86 and MHC-II expressions with a high antigen uptake ability and poor T-cell stimulatory function. [Sci Rep]
Full Article

E3 Ubiquitin Ligase Cbl-b Suppresses Proallergic T Cell Development and Allergic Airway Inflammation
The authors report that the loss of Cbl-b facilitates T helper 2 (Th2) and Th9 cell differentiation in vitro. In a mouse model of asthma, the absence of Cbl-b results in severe airway inflammation and stronger Th2 and Th9 responses. [Cell Rep] Abstract | Full Article | Graphical Abstract

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The Balance of Intestinal Foxp3⁺ Regulatory T Cells and Th17 Cells and Its Biological Significance
Researchers discuss the characteristics of gut regulatory T cells and Th17 cells and their role in gut diseases. [Expert Rev Clin Immunol] Abstract

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Grants Support Immunotherapy-Based Treatment for Childhood Cancer
Two Baylor College of Medicine researchers have received grants from the nonprofit organization Alex’s Lemonade Stand Foundation to advance their immunotherapy-based treatment approaches for childhood cancer from the bench to bedside. [Baylor College of Medicine] Press Release

NeoStem Expands Treg International Patent Portfolio with Granting of Patent in Japan
NeoStem, Inc. announced the expansion of intellectual property protection surrounding the Company’s T-regulatory cell (Treg) program with the grant of Japanese Patent Number 5409827 titled “Methods for the Isolation and Expansion of Cord Blood Derived T Regulatory Cells.” This grant further expands the scope and reach of NeoStem’s Treg patent estate internationally. [NeoStem, Inc.] Press Release

Coronado Biosciences Granted a Second Key Patent for CNDO-109, an Activator of Natural Killer Cells
Coronado Biosciences, Inc. announced the U.S. Patent and Trademark Office has granted a second key patent for CNDO-109 directed to the activated Natural Killer (NK) cell compositions employed in its NK cell therapy program, and has further issued a Notice of Allowance in an additional pending application directed to pharmaceutical compositions comprising these activated NK cells. [Coronado Biosciences, Inc.] Press Release

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