Human Immunology News Volume 4.38 | Sep 27 2016

TOP STORY

The Scaffolding Function of the RLTPR Protein Explains Its Essential Role for CD28 Co-Stimulation in Mouse and Human T Cells

Investigators demonstrated that RLTPR is essential for CD28 co-stimulation in human T cells and that its noncanonical pleckstrin-homology domain, leucine-rich repeat domain, and proline-rich region were mandatory for that task. [J Exp Med] Abstract

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Dual T Cell– and B Cell–Intrinsic Deficiency in Humans with Biallelic RLTPR Mutations

The authors report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, the mouse orthologue of which is essential for CD28 signaling. Their CD4⁺ T cells exhibit a “Th2” cell bias ex vivo and when cultured in vitro, contrasting with the paucity of “Th1,” “Th17,” and T follicular helper cells. [J Exp Med] Abstract

Identification of Tonsillar CD4⁺CD25⁻LAG3⁺ T Cells as Naturally Occurring IL-10-Producing Regulatory T Cells in Human Lymphoid Tissue

Researchers identified CD4⁺CD25⁻LAG3⁺ T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. [J Autoimmun] Abstract

Human Adenosine Deaminases ADA1 and ADA2 Bind to Different Subsets of Immune Cells

Investigators found that adenosine deaminase 2 (ADA2) binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4⁺ T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. [Cell Mol Life Sci] Abstract

Decreased IL7Rα and TdT Expression Underlie the Skewed Immunoglobulin Repertoire of Human B-Cell Precursors from Fetal Origin

The mechanisms underlying the restricted fetal immunoglobulin gene repertoire are currently unresolved. The authors addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. [Sci Rep] Full Article

Dopaminergic Receptors on CD4⁺ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson’s Disease

Since the mainstay of Parkinson’s disease (PD) treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, scientists examined CD4⁺ T naive and memory lymphocytes in PD patients and in healthy subjects, with specific regard to dopaminergic receptor expression. [Sci Rep] Full Article

miR-124a and miR-155 Enhance Differentiation of Regulatory T Cells in Patients with Neuropathic Pain

Researchers demonstrated that microRNAs (miRNAs) are involved in the differentiation of regulatory T cells in neuropathic pain. They identified miR-124a and miR-155 as direct repressors of the histone deacetylase sirtuin1 in primary human CD4⁺ cells. [J Neuroinflammation] Full Article

Tolerogenic Dendritic Cells Generated with Dexamethasone and Vitamin D3 Regulate Rheumatoid Arthritis CD4⁺ T-Cells Partly via TGF-β1

Scientists established a method to generate stable tolerogenic dendritic cells (tolDC) by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4⁺ T-cells. [Clin Exp Immunol] Abstract

Azithromycin Modulates Immune Response of Human Monocyte-Derived Dendritic Cells and CD4⁺ T Cells

Scientists investigated the ability of azithromycin to influence the function of human monocyte-derived dendritic cells and CD4⁺ T cells. [Int Immunopharmacol] Abstract

Indoleamine 2,3-Dioxygenase, by Degrading L-Tryptophan, Enhances Carnitine Palmitoyltransferase I Activity and Fatty Acid Oxidation, and Exerts Fatty Acid-Dependent Effects in Human Alloreactive CD4⁺ T-Cells

The effect of indoleamine 2,3-dioxygenase (IDO) on fatty acid β-oxidation in CD4⁺ T-cells was evaluated in human mixed lymphocyte reactions using the IDO inhibitor, 1-DL-methyl-tryptophan. [Int J Mol Med] Abstract

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Histone Posttranslational Modifications of CD4⁺ T Cell in Autoimmune Diseases

The authors put forward a review of core posttranslational modulations that regulate T cell function and differentiation in the immune system, with a special emphasis on histone modifications in different T helper cell subsets as well as in autoimmune diseases. [Int J Mol Sci] Full Article

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Clinical Data Support Mechanism of Action and Patient Selection Biomarker for Imprime PGG, Biothera Pharmaceutical’s Phase II Cancer Immunotherapy

Biothera Pharmaceuticals, Inc. announced the presentation of clinical data demonstrating the mechanism of action of Imprime PGG, the company’s Phase II cancer immunotherapy drug, in healthy human volunteers. [Press release from Biothera Pharmaceuticals, Inc. discussing research presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, New York City] Press Release

Infinity Presents Initial Clinical and New Preclinical Data on IPI-549

Infinity Pharmaceuticals, Inc. announced initial clinical and new preclinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. [Press release from Infinity Pharmaceuticals, Inc. discussing research presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, New York City] Press Release

ARMO BioSciences Announces Data Presentations

ARMO BioSciences, Inc. announced the presentation of new Phase Ib clinical data on the company’s lead investigational immuno-oncology drug AM0010 in combination with an anti-PD-1 checkpoint inhibitor in patients with renal cell carcinoma or non-small cell lung cancer. [Press release from ARMO BioSciences, Inc. discussing research presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, New York City] Press Release

MD Anderson Cancer Center and Adaptimmune Form Strategic Alliance to Advance Development of Immunotherapies Targeting Multiple Cancers

Adaptimmune Therapeutics plc and The University of Texas MD Anderson Cancer Center announced that they have entered into a multi-year strategic alliance designed to expedite the development of novel adoptive T-cell therapies for multiple types of cancer. [Adaptimmune Therapeutics plc] Press Release

Kite Pharma Announces Positive Topline KTE-C19 Data from ZUMA-1 Pivotal Trial in Patients with Aggressive Non-Hodgkin Lymphoma (NHL)

Kite Pharma, Inc. announced positive topline results from a pre-planned interim analysis of ZUMA-1 for its lead product candidate, KTE-C19, in patients with chemorefractory diffuse large B-cell lymphoma. [Kite Pharma, Inc.] Press Release

Bristol-Myers Squibb and Nektar Therapeutics Announce Oncology Clinical Collaboration to Evaluate the Combination of Opdivo (Nivolumab) and NKTR-214

Bristol-Myers Squibb Company and Nektar Therapeutics announced a new clinical collaboration to evaluate Bristol-Myers Squibb’s Opdivo with Nektar’s investigational medicine, NKTR-214, as a potential combination treatment regimen in five tumor types and seven potential indications. [Bristol-Myers Squibb Company] Press Release

X4 Pharmaceuticals Announces Initiation of Phase Ib Study of X4P-001 in Patients with Resectable Stage III and Stage IV Melanoma

X4 Pharmaceuticals announced dosing of the first patient in its Phase Ib study of X4P-001 in patients with resectable Stage III and Stage IV melanoma. [X4 Pharmaceuticals] Press Release

Zimbabwean Scientists Fight to Preserve National Academy

Following years of chronic funding shortages and political neglect, the Zimbabwe Academy of Science (ZAS) is on its knees and has made a plea for support from the large Zimbabwean diaspora. The academy has historically survived on donations and membership fees, but this is no longer sustainable, said ZAS head Christopher Mutambirwa at a meeting of Zimbabwean expatriates in Johannesburg, South Africa. At the moment, the ZAS’s activities are voluntary and unpaid. [Nature News] Editorial

Four Men and Two Women are Running for the Top Slot at the World Health Organization

The World Health Organization in Geneva, Switzerland, unveiled the names of the six candidates who are vying to succeed Margaret Chan as director-general. [Science Insider] Editorial

Worldwide Brain-Mapping Project Sparks Excitement — and Concern

In recent years, brain-mapping initiatives have been popping up around the world. They have different goals and areas of expertise, but now researchers will attempt to apply their collective knowledge in a global push to more fully understand the brain. [Nature News] Editorial

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