Immune Regulation News Volume 5.13 | Apr 12 2013

Autoimmune Pancreatitis in MRL/Mp Mice Is a T Cell-Mediated Disease Responsive to Cyclosporine A and Rapamycin Treatment
The authors report that blockage of CTLA-4 in MRL/Mp mice suppressed regulatory T cell function and raised the effector T cell response with subsequent histomorphological organ destruction, indicating that autoimmune pancreatitis is a T cell-driven disease. Using an established histopathological score, they found that dexamethasone, cyclosporine A and rapamycin, but less so azathioprine, reduced pancreatic damage. [Gut] Abstract

Excessive Th1 Responses Due to the Absence of TGF-β Signaling Cause Autoimmune Diabetes and Dysregulated Treg Cell Homeostasis
TGF-β signaling in T cells is critical for peripheral T-cell tolerance by regulating effector CD4+ T helper (Th) cell differentiation. However, it is still controversial to what extent TGF-β signaling in Foxp3+ regulatory T (Treg) cells contributes to immune homeostasis. Researchers showed that abrogation of TGF-β signaling in thymic T cells led to rapid type 1 diabetes development in NOD mice transgenic for the BDC2.5 T-cell receptor. [Proc Natl Acad Sci USA] Abstract

Inhibition of PDE4B Suppresses Inflammation by Increasing Expression of the Deubiquitinase CYLD
The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defense response. Researchers showed that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. [Nat Commun] Abstract | Press Release

Regulatory T Cells Prevent Plaque Disruption in Apolipoprotein E-Knockout Mice
Investigators report that adoptive transfer of regulatory T cells dose-dependently changed plaque composition to a stable plaque phenotype and lowered the incidence of plaque disruption in apolipoprotein E-knockout mice. The major mechanisms involved reduced expression of inflammatory cytokines and matrix metalloproteinase (MMP)-2 and MMP-9, and enhanced expression of P4Hα1 in the carotid plaque. [Int J Cardiol] Abstract

GARP-TGF-β Complexes Negatively Regulate Regulatory T Cell Development and Maintenance of Peripheral CD4⁺ T Cells In Vivo
Researchers address the role of Glycoprotein A Repetitions Predominant (GARP) in regulating regulatory T cells and conventional T cell development and immune suppression in vivo using a transgenic mouse expressing GARP on all T cells. They found that, despite forced expression of GARP on all T cells, stimulation through the TCR was required for efficient localization of GARP to the cell surface. [J Immunol] Abstract

Fine-Tuning of Regulatory T Cell Function: The Role of Calcium Signals and Naive Regulatory T Cells for Regulatory T Cell Deficiency in Multiple Sclerosis
As regulatory T cells (Tregs) counteract the sustained elevation of intracellular calcium, which is indispensable for full activation of conventional T cells (Tcons), the authors hypothesized that interference with this pathway might prompt multiple sclerosis-related Treg dysfunction. Using single-cell live imaging, they observed that Tregs rapidly reduce Ca²⁺ influx and downstream signals in Tcons upon cell contact, yet differ in their potency to efficiently suppress several target cells at the same time. [J Immunol] Abstract

Systems Model of T Cell Receptor Proximal Signaling Reveals Emergent Ultrasensitivity
Researchers used a systems model to show that signaling architecture produces emergent ultrasensitivity resulting in switch-like responses at the scale of individual T cell antigen receptors. Importantly, this switch-like response is an emergent property, so that removal of multiple immunoreceptor tyrosine-based activation motifs, sequential phosphorylation, or differential affinities abolishes the switch. [PLoS Comput Biol]
Full Article

Decreased Regulatory T-Cells and CD4⁺/CD8⁺ Ratio Correlate with Disease Onset and Progression in Patients with Generalized Vitiligo
Scientists evaluated CD4⁺/CD8⁺ ratio and CD4⁺CD25^hiFoxP3⁺ regulatory T cells (Tregs) in Generalized Vitiligo (GV) patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4⁺/CD8⁺ ratio and Tregs in 82 patients and 50 controls. CD8⁺ T-cell counts were significantly higher in GV patients as compared to controls. [Pigment Cell Melanoma Res] Abstract

Sex Bias in Experimental Immune-Mediated, Drug-Induced Liver Injury in BALB/c Mice: Suggested Roles for Tregs, Estrogen, and IL-6
Immune regulation by CD4⁺CD25⁺FoxP3⁺ regulatory T-cells (Tregs) and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, researchers investigated their role in a mouse model of immune-mediated drug-induced liver injury. [PLoS One] Full Article

The Hedgehog Receptor Patched1 in T Cells Is Dispensable for Adaptive Immunity in Mice
Hedgehog (Hh) signaling modulates T cell development and function but its exact role remains a matter of debate. To further address this issue, researchers made use of conditional knock-out mice in which the Hh receptor Patched1 is inactivated in the T cell lineage. [PLoS One] Full Article

Modulating T Regulatory Cells in Cancer: How Close Are We?
The authors provide a historical perspective of the discovery of regulatory T cells (Tregs), followed by a summary of the existing literature on the role of Tregs in malignancy. [Immunol Cell Biol] Abstract

Importance of Reverse Signaling of the TNF Superfamily in Immune Regulation
F-related ligands (with the exception of lymphotoxin-α) are synthesized as type II transmembrane proteins, though many of them also have soluble forms. An increasing number of publications report that these ‘ligands’ behave as receptors, activating intracellular signaling pathways when interacting with cognate ‘receptors’ or agonistic antibodies. [Expert Rev Clin Immunol] Abstract

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

Immunotherapies against Cancer: German Cancer Research Center to Broaden Strategic Alliance with Bayer HealthCare
The German Cancer Research Center and Bayer HealthCare will extend their successful strategic research alliance in search of novel cancer therapeutics by focusing their activities also on the field of immunotherapy. [German Cancer Research Center] Press Release

Pitt Team Gets $5 Million National Institutes of Health Grant to Make Vaccine Component that Stimulates TB-Fighting T-Cells
Researchers at the University of Pittsburgh School of Medicine have received a $5 million federal grant to develop a vaccine ingredient that can generate the type of immune response needed to protect against tuberculosis (TB) infection. [UPMC/University of Pittsburgh Schools of the Health Sciences] Press Release

T Cell Biology Pioneer Allison Wins First AACR Honor for Cancer Immunology
The scientist whose discoveries led to the first drug approved for metastatic melanoma by “treating the immune system, not the cancer,” also is the first to receive the AACR-CRI Lloyd J. Old Award in Cancer Immunology. James Allison, Ph.D., professor and chair of The University of Texas MD Anderson Cancer Center Department of Immunology, was honored at the AACR Annual Meeting 2013 in Washington, D.C. [The University of Texas MD Anderson Cancer Center] Press Release

Immune Therapy from Austria Receives Orphan Drug Designation from European Medicines Agency
The European Medicines Agency recently awarded the Austrian biotech company Activartis an Orphan Drug Designation for its innovative Cancer Immune Therapy AV0113. The Orphan Drug Designation applies specifically to the use of AV0113 for the treatment of glioma, a type of brain tumor, which afflicts around one in 10.000 people in the EU. [Activartis Biotech GmbH] Press Release

From our sponsors:
View immunology lectures, protocols and other resources on the Human Immunology Portal.

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)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

PhD Studentship – Mucosal immunology (KU Leuven Translational Research Center for Gastrointestinal Disorders)

PhD Candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – Immunology (Institut Pasteur)

Postdoctoral Fellow – Immunotherapeutics in Childhood Cancer (Perelman School of Medicine at the University of Pennsylvania)

Postdoctoral Position – Type 1 Diabetes and Systemic Lupus Erythematosus (University of Florida)

PhD Student/ Early Stage Researcher – T Cell Regulation (The Netherlands Cancer Institute [NKI-AvL])

PhD Studentship – Thymic Dendritic Cells and Regulation of T-Cell Development (University of Birmingham / MRC Centre for Immune Regulation)

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.

Have we missed an important article or publication in Immune Regulation News? Click here to submit!

Comments or Suggestions? Email info@connexoncreative.com with your feedback.