Immune Regulation News Volume 5.24 | Jun 28 2013

Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T Helper 1 and T Helper 2 Cell Polarization
Naive CD4⁺ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, scientists generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hours of in vitro polarization toward T helper 1 and T helper 2 cell lineages. [Immunity] Abstract | Graphical Abstract

Tob1 Plays a Critical Role in the Activation of Encephalitogenic T Cells in CNS Autoimmunity
Investigators report that experimental autoimmune encephalomyelitis (EAE) in Tob1^-/- mice was associated with augmented central nervous system (CNS) inflammation, increased infiltrating CD4⁺ and CD8⁺ T cell counts, and increased myelin-reactive Th1 and Th17 cells, with reduced numbers of regulatory T cells. [J Exp Med] Abstract | Press Release

Shp1 Regulates T Cell Homeostasis by Limiting IL-4 Signals
To define the T cell-intrinsic role of Shp1, researchers characterized mice with a T cell-specific Shp1 deletion (Shp1^fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1^fl/fl CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4⁺ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. [J Exp Med] Abstract

Melanoma Immunotherapy Using Mature DCs Expressing the Constitutive Proteasome
Since proteasomes generate peptides presented by HLA class I molecules, the authors hypothesized that mature melanoma antigen-loaded DCs engineered to process antigens through constitutive proteasomes would be superior inducers of antimelanoma immunity in vivo. [J Clin Invest] Full Article

Dysfunctional CD39^POS Regulatory T Cells and Aberrant Control of T Helper Type 17 Cells in Autoimmune Hepatitis
Investigators described multiple CD39^pos regulatory T cell defects that potentially contribute to the impaired immuno-regulation that is characteristic of autoimmune hepatitis. [Hepatology] Abstract

Plasmid-Encoded Proinsulin Preserves C-Peptide while Specifically Reducing Proinsulin-Specific CD8⁺ T Cells in Type 1 Diabetes
Scientists hypothesized that an engineered DNA plasmid encoding proinsulin (BHT-3021) would preserve β cell function in type 1 diabetes patients through reduction of insulin-specific CD8⁺ T cells. Proinsulin-reactive CD8⁺ T cells, but not T cells against unrelated islet or foreign molecules, declined in the BHT-3021 arm. No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. [Sci Transl Med] Abstract | Press Release

IL-22-Producing Neutrophils Contribute to Antimicrobial Defense and Restitution of Colonic Epithelial Integrity during Colitis
Using a dextran sodium sulfate-induced mouse model of acute colitis, the authors observed an interleukin (IL)-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. [Proc Natl Acad Sci USA] Abstract

CC-Chemokine Receptor 8 Potentiates Donor T_reg Survival and Is Critical for the Prevention of Murine Graft-versus-Host Disease
Previous work suggested that early T_reg migration into lymphoid tissue was important for graft-versus-host disease (GvHD) prevention. However, it is unclear how and where T_regs function longitudinally to affect GvHD. To better understand their mechanism of action, researchers studied two T_reg-associated chemokine receptors in murine stem cell transplant models. [Blood] Abstract

Downregulation of Stat3 in Melanoma: Reprogramming the Immune Microenvironment as an Anticancer Therapeutic Strategy
Researchers investigated whether lentiviral (LV) delivery of Stat3-targeting short hairpin RNA (shRNA; LV-shStat3) to K1735-C4 melanoma cells modulates antitumor immunity. A single injection of LV-shStat3 in K1735-C4 tumors efficiently downregulated Stat3 in vivo and resulted in reduction of both vascular endothelial growth factor secretion and in myeloid-derived suppressor cell (MDSC) numbers. In contrast, the authors observed an increase in interleukin-6 and interferon-γ secretion, mature dendritic cells (DCs) and CD8⁺ T cells. Both DCs and CD8⁺ T cells displayed enhanced activity, whereas granulocytic MDSCs lost their suppressive capacity upon Stat3 downregulation. [Gene Ther] Abstract

Myeloid-Derived Suppressor Cells in Cancer: Recent Progress and Prospects
Immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs) and T regulatory cells, downregulate antitumour immunity and cancer immunotherapy. In this article, the authors review data concerning the phenotypical and functional role of MDSCs in cancers. [Immunol Cell Biol] Abstract

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

Prima BioMed to Move Forward with Phase II Clinical Program for CVac in Pancreatic, Colorectal, and Triple-Negative Breast Cancers
Prima BioMed Ltd announced that it will move forward with three separate phase II clinical trials to evaluate the potential of CVac™ for the treatment of resectable pancreatic cancer, metastatic colorectal cancer, and triple-negative breast cancer. CVac is Prima’s lead product, a personalized immunocellular therapy targeted at mucin 1 overexpressing cancer cells, and in late phase trials for the treatment of epithelial ovarian cancer in remission. [Prima BioMed Ltd] Press Release

From our sponsor: Free mouse hematopoietic progenitors wallchart. Request your copy.

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)  

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

NEW Postdoctoral Position – Complement System in Acute and Chronic Inflammatory Diseases (Institute for Systemic Inflammation Research, University of Lübeck)

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.)

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)

Recruit Top Talent: Reach more than 50,000 potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.