Immune Regulation News Volume 3.16 | May 6 2011

Nanovaults Used to Prod Immune System to Fight Cancer
UCLA scientists have discovered a way to “wake up” the immune system to fight cancer by delivering an immune system–stimulating protein in a nanoscale container called a vault directly into lung cancer tumors. [Press release from the University of California, Los Angeles discussing online prepublication in PLoS ONE]

Antibodies Help Protect Monkeys from HIV-Like Virus, NIH Scientists Show
Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). [Press release from the National Institute of Allergy and Infectious Diseases discussing online prepublication in Science Translational Medicine]

New Structure of an Important Immune System Complex Resolves a 10-Year Controversy
Researchers have resolved a longstanding controversy surrounding an important structure of the immune system that could result in new therapeutic targets for antibody-mediated autoimmune diseases as well as the potential to enhance the efficacy of vaccines. [Press release from the University of Toronto discussing online prepublication in Science]

Yale Researchers Identify Four Key Weapons in Immune System’s Arsenal
Yale University researchers have identified four unique host defense proteins among thousands that seem to play a crucial role in mobilizing the immune system’s response to bacterial infections. [Press release from Yale University discussing online prepublication in Science]

Wistar Researchers: Direct Proof of How T Cells Stay in “Standby” Mode
For years, scientists have wondered if quiescence occurred by default or whether T cells need to work at remaining silent. Now, researchers provide the first direct proof that a protein, called Foxp1, actively maintains this state of quiescence in T cells until the cells are called upon by other parts of the immune system. [Press release from The Wistar Institute discussing online prepublication in Nature Immunology]

Birmingham Scientists Discover ‘How to Stop Your Immune System from Killing You’
Research findings show how a protein, called CTLA-4, keeps the immune system damped down during day-to-day activities and prevents inappropriate aggressive behaviour from T cells, the ‘command centre of our immune response’. [Press release from the University of Birmingham discussing online prepublication in Science]

The Soul of a Cell: Researchers Used Advanced Instrument to Read Cells’ Minds
Researchers have taken a machine already in use for the measurement of impurities in semiconductors and used it to analyze immune cells in far more detail than has been possible before. [Press release from the Stanford University School of Medicine discussing online prepublication in Science]

A Crystal Structure of the Complex Between Human Complement Receptor 2 and Its Ligand C3d
Researchers now report a cocrystal structure of a CR2(SCR1-2):C3d complex at 3.2 angstrom resolution in which the interaction interfaces differ markedly from the previously published structure and are consistent with the biochemical data. [Science]

A Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection
Here, researchers examined a complete mouse 65-kilodalton guanylate-binding protein gene family as part of a 43-member IFN-γ–inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. [Science]

Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4
Here, researchers show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4–expressing cells, resulting in impaired costimulation via CD28. [Science]

Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum
Such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention. [Science]

Identification of T Helper Type 1–Like, Foxp3+ Regulatory T Cells in Human Autoimmune Disease
Here researchers describe a higher frequency of T helper type 1-like, interferon-γ-secreting Foxp3+ T cells in untreated subjects with relapsing remitting multiple sclerosis as compared to healthy control individuals. [Nat Med]

Transcription Factor Foxp1 Exerts Essential Cell-Intrinsic Regulation of the Quiescence of Naive T Cells
Here researchers report that mature naive CD8+ T cells lacking the transcription factor Foxp1 gained effector phenotype and function and proliferated directly in response to interleukin 7 (IL-7) in vitro. [Nat Immunol]

Protective Capacity of Memory CD8+ T Cells Is Dictated by Antigen Exposure History and Nature of the Infection
Herein, researchers show that secondary (boosted) memory CD8+ T cells were better than primary memory CD8+ T cells in controlling some, but not all acute infections with diverse pathogens. [Immunity]

A Cluster of Coregulated Genes Determines TGF-β–Induced Regulatory T-Cell (Treg) Dysfunction in NOD Mice
Researchers find that TGF-regulatory T cells (Tregs) derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. [Proc Natl Acad Sci USA]

Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth
Researchers are assessing the efficacy of intratumoral injection of dendritic cells (DC) transduced with an adenoviral vector expressing the secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial in advanced non-small cell lung cancer (NSCLC). [PLoS ONE]

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys
Researchers used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). [Sci Transl Med]