Immune Regulation News Volume 4.48 | Dec 14 2012

Bcl11a Is Essential for Lymphoid Development and Negatively Regulates p53
Researchers report that in the adult mouse, Bcl11a is expressed in most hematopoietic cells and is highly enriched in B cells, early T cell progenitors, common lymphoid progenitors, (CLPs) and hematopoietic stem cells (HSCs). In the adult mouse, Bcl11a deletion causes apoptosis in early B cells and CLPs and completely abolishes the lymphoid development potential of HSCs to B, T, and NK cells. [J Exp Med]
Abstract | Press Release

L-Asparaginase II Produced by Salmonella Typhimurium Inhibits T Cell Responses and Mediates Virulence
Investigators showed that S. Typhimurium inhibit T cell responses by producing L-Asparaginase II, which catalyzes the hydrolysis of L-asparagine to aspartic acid and ammonia. L-Asparaginase II is necessary and sufficient to suppress T cell blastogenesis, cytokine production, and proliferation and to downmodulate expression of the T cell receptor. [Cell Host Microbe] Abstract

A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans
The authors investigated the immunodominant CD4+ T-cell response to neuraminyllactose-binding hemagglutinin (HpaA)- a conserved, H. pylori-specific colonization factor that is being investigated as an antigen for vaccination strategies. [Gastroenterology] Abstract

Activation, Exhaustion and Persistent Decline of the Anti-Microbial MR1-Restricted MAIT Cell Population in Chronic HIV-1 Infection
Mucosal-associated invariant T (MAIT) cells are CD161+, express a Vα7.2 TCR, are primarily CD8+ and numerous in blood and mucosal tissues. Their role in HIV-1 infection is unknown. Researchers found levels of MAIT cells to be severely reduced in circulation in patients with chronic HIV-1 infection. Residual MAIT cells were highly activated and functionally exhausted. [Blood] Abstract

Crosstalk between Immune Cell and Oncolytic Vaccinia Therapy Enhances Tumor Trafficking and Antitumor Effects
Scientists previously developed several strategies for optimizing the delivery of oncolytic vaccinia virus vectors to their tumor targets, including the use of immune cell-based carrier vehicles and the incorporation of mutations that increase production of the enveloped form of vaccinia (extracellular enveloped viral (EEV)) that is better adapted to spread within a host. Here, they initially combined these approaches to create a novel therapeutic, consisting of an immune cell preloaded with an oncolytic virus that is EEV enhanced. [Mol Ther] Abstract

IFN-γ from CD4 T Cells Is Essential for Host Survival and Enhances CD8 T Cell Function during Mycobacterium tuberculosis Infection
Researchers sought to determine whether IFN-γ from sources other than CD4 T cells was sufficient to control M. tuberculosis infection and whether CD4 T cells had a role in addition to IFN-γ production. To investigate the role of IFN-γ from CD4 T cells, a murine adoptive transfer model was developed in which all cells were capable of producing IFN-γ, with the exception of CD4 T cells. [J Immunol] Abstract

Mycobacterium tuberculosis Controls miR-99b Expression in Infected Murine Dendritic Cells to Modulate Host Immunity
Investigators showed that miRNA-99b (miR-99b) plays a key role in the pathogenesis of Mycobacterium tuberculosis (M. tb) infection. They found that miR-99b expression was highly up-regulated in M. tb strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. [J Biol Chem] Abstract | Full Article

Mobilization of Regulatory T Cells in Response to Carotid Injury Does Not Influence Subsequent Neointima Formation
T cells have been attributed an important role in modulating repair responses following vascular injury. The authors investigated the role of different T cell subsets in this context. [PLoS One] Full Article

IL-27 Increases BST-2 Expression in Human Monocytes and T Cells Independently of Type I IFN
To characterize anti-viral genes modulated by IL-27, the authors examined interferon (IFN)-responsive gene: tetherin/bone marrow stromal cell antigen 2 (BST-2). Results showed that IL-27 can directly induce BST-2 expression, independently of an intermediary type I IFN response. [Sci Rep] Full Article

The Where and When of T Cell Regulation in Transplantation
The activation and homing characteristics of regulatory T cells (Tregs) are important to their regulatory capabilities, with activation and homing occurring in the same time and space as conventional T cells. This review discusses these characteristics and recent advances in the field as we move closer to the ultimate goal of utilizing Tregs as treatment for allograft rejection and graft-versus-host disease. [Trends Immunol] Abstract

Immunoregulation through Membrane Proteins Modified by Reducing Conditions Induced by Immune Reactions
The authors summarize the recent advances in understanding the conditions that lead to disulfide bond reduction in membrane proteins and their effects in regulating immune function. [Eur J Immunol] Abstract

Leukemia Patients Remain in Remission More than Two Years after Receiving Genetically Engineered T Cell Therapy
Nine of twelve leukemia patients who received infusions of their own T cells after the cells had been genetically engineered to attack the patients’ tumors responded to the therapy, which was pioneered by scientists in the Perelman School of Medicine at the University of Pennsylvania. [Press release from The Perelman School of Medicine discussing research to be presented at the American Society of Hematology’s Annual Meeting, Atlanta] Press Release

NKT Therapeutics Presents Data on Potential Antibody Treatment for Sickle Cell Disease
NKT Therapeutics, Inc. announced preclinical study results supporting the potential of its lead therapeutic candidate, NKTT120, as an innovative approach to the treatment of sickle cell disease. Preclinical studies of NKTT120, a humanized monoclonal antibody, showed its ability to generate a safe, rapid, specific and complete depletion of invariant Natural Killer T cells 24 hours post dosing, thus offering a means to reduce the chronic inflammation associated with sickle cell disease pathology. [Press release from NKT Therapeutics, Inc. discussing research presented at the American Society of Hematology’s Annual Meeting, Atlanta] Press Release | Abstract

UT MD Anderson, GlaxoSmithKline to Collaborate on New Approach to Cancer Immune Therapy; Success Could Earn Cancer Center $335 Million Plus Royalties
The University of Texas (UT) MD Anderson Cancer Center and GlaxoSmithKline (GSK) have signed a research collaboration and license agreement to develop new therapeutic antibodies that promote an immune system attack against cancer. Under terms of the agreement, MD Anderson grants GSK exclusive worldwide rights to develop and commercialize the antibodies, which activate OX40 on the surface of T cells. [The University of Texas MD Anderson Cancer Center] Press Release

SU2C and CRI Announce New Immunology Translational Research Dream Team
Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) announce the formation of a Dream Team project dedicated to cancer immunology – “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy.” The Dream Team will receive $10 million in funding over three years for this translational cancer research project that will unite laboratory and clinical efforts leading to the immunological treatment, control and prevention of cancer.  [Stand Up To Cancer] Press Release

SLU Researchers Win NIH Grant to Study Lupus
Two researchers at Saint Louis University’s (SLU) division of rheumatology in the department of internal medicine have been awarded a $1.8 million NIH grant to study the physiological and biochemical functions in lupus, an autoimmune disease, and develop possible new medications for its treatment. [Saint Louis University] 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)

NEW Frontiers in Immunology and Inflammation: From Molecules to Disease
February 12-13, 2013
Tokyo, Japan

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