Immune Regulation News Volume 8.08 | Mar 4 2016

Control of T Cell Antigen Reactivity via Programmed TCR Downregulation
Investigators found that activated CD4⁺ T cells, at the peak of clonal expansion, persistently downregulated their T cell antigen receptor (TCR) expression in proportion to the strength of the initial antigen recognition. [Nat Immunol] Abstract

IFN-Gamma and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma
The authors report that IFN-gamma and CCL2 released systemically in response to a CD40 agonist cooperate to redirect a subset of Ly6C⁺CCR2⁺ monocytes/macrophages to infiltrate tumors and deplete fibrosis. [Cancer Discov] Abstract | Press Release

Dendritic Cell Vaccines Based on Immunogenic Cell Death Elicit Danger Signals and T Cell–Driven Rejection of High-Grade Glioma
Researchers combined dendritic cell (DC) immunotherapy with immunogenic cell death (ICD) induced by hypericin-based photodynamic therapy. In an orthotopic high-grade glioma (HGG) mouse model involving prophylactic/curative setups, both biologically and clinically relevant versions of ICD-based DC vaccines provided strong anti-HGG survival benefit. [Sci Transl Med] Abstract | Press Release

EAF2 Mediates Germinal Center B-Cell Apoptosis to Suppress Excessive Immune Responses and Prevent Autoimmunity
The authors showed that ELL-associated factor 2 (EAF2) is selectively upregulated in germinal center (GC) B cells among various immune cell types and promotes apoptosis of GC B cells both in vitro and in vivo. [Nat Commun] Full Article

Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain
Researchers identified neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35–55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. [J Neurosci] Abstract | Press Release

T Follicular Helper Expansion and Humoral-Mediated Rejection Are Independent of the HVEM/BTLA Pathway
Scientists assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator (HVEM/BTLA) signaling pathway in the context of antibody-mediated allograft rejection. [Cell Mol Immunol] Abstract

CD19xCD3 DART Protein Mediates Human B-Cell Depletion In Vivo in Humanized BLT Mice
Scientists present findings of specific and systemic human B-cell depletion by a CD19xCD3 dual-affinity re-targeting (DART) protein in humanized BLT mice. Administration of the CD19xCD3 DART protein resulted in a dramatic sustained depletion of human CD19⁺ B cells from the peripheral blood, as well as a dramatic systemic reduction of human CD19⁺ B-cell levels in all tissues analyzed. [Mol Ther Oncolytics] Full Article

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Lilly Receives Positive CHMP Opinion for Ixekizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis
Eli Lilly and Company announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion for ixekizumab for the treatment of moderate-to-severe plaque psoriasis in adults in the European Union who are candidates for systemic therapy. [Eli Lilly and Company] Press Release

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