Featured
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Letter |
Metabolic maintenance of cell asymmetry following division in activated T lymphocytes
The asymmetric distribution of mTORC1 and c-Myc in the first division of daughter cells of activated CD8 T cells affects the proliferation, metabolism and differentiation potential of their progeny.
- Katherine C. Verbist
- , Cliff S. Guy
- & Douglas R. Green
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Letter |
Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
Modulating cholesterol metabolism can improve CD8+ T-cell-mediated immunity against tumours; genetic or pharmacological inhibition of the cholesterol esterification enzyme ACAT1 led to higher plasma membrane cholesterol levels, better T-cell receptor clustering and signalling, improved immunological synapse maturation, and enhanced antitumour activity in mice.
- Wei Yang
- , Yibing Bai
- & Chenqi Xu
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Article |
Immune homeostasis enforced by co-localized effector and regulatory T cells
Autoantigen-presenting dendritic cells are shown to interact with both effector and regulatory T cells, and effector-produced IL-2 activates the transcription factor STAT5 in regulatory T cells, which in turn upregulates suppressive molecules and prevents autoimmunity.
- Zhiduo Liu
- , Michael Y. Gerner
- & Ronald N. Germain
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Letter |
T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
CD8 T-cell exhaustion, although a negative prognostic indicator during persistent infections, is shown to be associated with a good outcome in autoimmune and inflammatory diseases.
- Eoin F. McKinney
- , James C. Lee
- & Kenneth G. C. Smith
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Letter |
T–B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction
Interactions between T and B cells in the germinal centre are brief but involve extensive cell-surface contact in an entangled mode; ICOSL promotes T–B entanglement and B-cell acquisition of CD40L, which drives B cells to upregulate ICOSL, thus forming an intercellular feed-forward loop that is required for efficient positive selection and development of the bone marrow plasma cell compartment.
- Dan Liu
- , Heping Xu
- & Hai Qi
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Letter |
Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development
Here, the helix–loop–helix transcription factor Ascl2 is shown to be critically important for the initiation of follicular T-helper-cell development and the germinal centre response.
- Xindong Liu
- , Xin Chen
- & Chen Dong
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Outlook |
Calling cells to arms
Increased understanding of immune- and tumour-cell biology has led to an explosion of research into potential ways to harness the immune system to kill cancer. By Emily Elert.
- Emily Elert
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Outlook |
Adoptive cell therapy: Honing that killer instinct
Genetically altered immune cells are helping to push life-threatening cancers into remission and generating a buzz.
- Courtney Humphries
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Letter |
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
In mice, provision of butyrate—a short-chain fatty acid produced by commensal microorganisms during starch fermentation—facilitates extrathymic generation and differentiation of Foxp3+ regulatory T cells, demonstrating that metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells.
- Nicholas Arpaia
- , Clarissa Campbell
- & Alexander Y. Rudensky
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Outlook |
Vaccines: An age-old problem
Researchers are on the hunt for a better alternative to the BCG vaccine.
- Sarah DeWeerdt
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Outlook |
Latency: A sleeping giant
Most people infected with Mycobacterium tuberculosis never get the disease, but predicting who will is turning out to be a complex problem.
- Courtney Humphries
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Letter |
Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis
Neuropilin-1 (Nrp1) on regulatory T (Treg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of Treg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient Treg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.
- Greg M. Delgoffe
- , Seng-Ryong Woo
- & Dario A. A. Vignali
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Letter |
mTORC1 couples immune signals and metabolic programming to establish Treg-cell function
Here, mTORC1-dependent lipogenic programming is shown to be important for regulatory T-cell function, in part through the upregulation of the effector molecules CTLA4 and ICOS.
- Hu Zeng
- , Kai Yang
- & Hongbo Chi
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Letter |
BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
Diverse autoimmune and allergic diseases are associated with polymorphisms in a locus encoding the transcription factor BACH2; here, BACH2 is shown to be a broad regulator of immune activation that stabilizes the differentiation of Treg cells by repressing commitment of CD4+ T cells to alternate cell fates.
- Rahul Roychoudhuri
- , Kiyoshi Hirahara
- & Nicholas P. Restifo
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Letter |
Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility
ICOS ligand expression by bystander B cells is shown to induce pseudopod extension and migration of CXCR5-expressing T-helper cells into B-cell follicles, where they provide help to cognate B cells for germinal centre development.
- Heping Xu
- , Xuanying Li
- & Hai Qi
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Letter |
Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids
Calcium–lipid electrostatic interactions are shown to amplify the tyrosine phosphorylation of CD3ε and CD3ζ in T-cell antigen receptor complex.
- Xiaoshan Shi
- , Yunchen Bi
- & Chenqi Xu
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Article |
Novel Foxo1-dependent transcriptional programs control Treg cell function
The results of a series of genetic experiments indicate that Foxo1 has a pivotal, Foxp3-independent role controlling regulatory T-cell function.
- Weiming Ouyang
- , Will Liao
- & Ming O. Li
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Letter |
A vaccine strategy that protects against genital herpes by establishing local memory T cells
A genital herpes simplex vaccine strategy of immunization using attenuated virus with peripheral local chemokine application can establish a population of protective tissue-resident memory T cells.
- Haina Shin
- & Akiko Iwasaki
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Letter |
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation
A genetically engineered mouse model is used to determine the mechanism of acquired resistance to adoptive therapy with cytotoxic T cells specific for a melanocytic differentiation antigen; tumour necrosis factor (TNF)-α is identified as a crucial factor that causes reversible dedifferentiation of mouse and human melanoma cells.
- Jennifer Landsberg
- , Judith Kohlmeyer
- & Thomas Tüting
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News & Views |
Tolerating pregnancy
The activity of specific suppressive immune cells, some of which persist to aid subsequent pregnancies, helps to explain how a pregnant female's immune system tolerates fetal antigens inherited from the father. See Letter p.102
- Alexander G. Betz
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Letter |
HIV-infected T cells are migratory vehicles for viral dissemination
Using intravital microscopy, this study visualizes HIV-1-infected T cells within the lymph nodes of humanized mice, demonstrating that infected cells have reduced motility and long membrane processes; treating infected mice with a lymphocyte egress inhibitor prevents HIV-1 from spreading to the circulation during the course of treatment.
- Thomas T. Murooka
- , Maud Deruaz
- & Thorsten R. Mempel
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Research Highlights |
Human response in model mice
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Research Highlights |
How fat spurs inflammation
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Research Highlights |
A race to kill or be killed
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Letter |
Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
Local skin infection is shown to generate long-lived T cells that reside throughout the skin and are potent effector cells, superior to circulating memory T cells in providing rapid long-term protection again cutaneous re-infection.
- Xiaodong Jiang
- , Rachael A. Clark
- & Thomas S. Kupper
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Letter |
Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting
Exome analysis of chemical-carcinogen-induced mouse tumours provides evidence for T-cell-mediated immunoselection as a mechanism of immunoediting.
- Hirokazu Matsushita
- , Matthew D. Vesely
- & Robert D. Schreiber
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Letter |
Response to self antigen imprints regulatory memory in tissues
Thymus-derived regulatory T cells are activated by recognition of peripheral self antigen, persist in the target tissue on cessation of antigen exposure, and respond to re-exposure to self antigen with enhanced functional activity.
- Michael D. Rosenblum
- , Iris K. Gratz
- & Abul K. Abbas
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Letter |
Natural killer cells act as rheostats modulating antiviral T cells
Natural killer cells can act as rheostats, or ‘master regulators’, controlling antiviral T-cell responses.
- Stephen N. Waggoner
- , Markus Cornberg
- & Raymond M. Welsh
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Research Highlights |
T cell makes nerve molecule
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News |
How microbes train our immune system
Gut bacteria coax T cells to see them as friends.
- Alla Katsnelson
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Letter |
Different patterns of peripheral migration by memory CD4+ and CD8+ T cells
- Thomas Gebhardt
- , Paul G. Whitney
- & Scott N. Mueller
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Letter |
A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
- Vlad C. Seitan
- , Bingtao Hao
- & Matthias Merkenschlager
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Article |
A critical role for TCF-1 in T-lineage specification and differentiation
- Brittany Nicole Weber
- , Anthony Wei-Shine Chi
- & Avinash Bhandoola
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Article |
Second messenger role for Mg2+ revealed by human T-cell immunodeficiency
- Feng-Yen Li
- , Benjamin Chaigne-Delalande
- & Michael J. Lenardo
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Letter |
Control of TH17 cells occurs in the small intestine
- Enric Esplugues
- , Samuel Huber
- & Richard A. Flavell
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Letter |
Intravenous gammaglobulin suppresses inflammation through a novel TH2 pathway
- Robert M. Anthony
- , Toshihiko Kobayashi
- & Jeffrey V. Ravetch
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Letter |
In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche
- Joji Fujisaki
- , Juwell Wu
- & Charles P. Lin
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Letter |
Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine
- Scott G. Hansen
- , Julia C. Ford
- & Louis J. Picker
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News & Views |
A helping hand against autoimmunity
The TH17 helper cells of the immune system have a dark side: they mediate autoimmune disorders. Two drugs that prevent the differentiation and activity of these cells might be of therapeutic value. See Letters p.486 & p.491
- Anton M. Jetten
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Letter |
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand
- Laura A. Solt
- , Naresh Kumar
- & Thomas P. Burris
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Letter |
Dampening of death pathways by schnurri-2 is essential for T-cell development
The zinc-finger-containing protein schnurri-2 is shown to regulate positive selection in T-cell development by dampening the mitochondrial death pathway.
- Tracy L. Staton
- , Vanja Lazarevic
- & Laurie H. Glimcher
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Letter |
Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection
This study shows that memory T-cell activation in viral infection occurs, in part, by cross-dressing; that is, the transfer of loaded MHC-peptide molecules from an infected cell to dendritic cells.
- Linda M. Wakim
- & Michael J. Bevan
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Letter |
Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity
- Jun R. Huh
- , Monica W. L. Leung
- & Dan R. Littman
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News & Views |
Conditional stability of T cells
Data from several recent studies on the dynamics of regulatory T cells — which suppress excessive immune responses — do not add up. Collective analysis of the observations may reconcile the differences between them.
- Shimon Sakaguchi
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Letter |
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
CD4+ T cells that selectively produce interleukin (IL)-17 (TH17 cells) are essential for host defence and autoimmunity. It has been thought that IL-6 and transforming growth factor (TGF)-β1 are the factors responsible for initiating the specification of TH17 cells. Here, however, it is shown that TH17 differentiation can occur in the absence of TGF-β signalling. IL-6, IL-23 and IL-1β effectively induced IL-17 production in naive precursors. These data reveal an alternative mode for TH17 differentiation and the importance of IL-23.
- Kamran Ghoreschi
- , Arian Laurence
- & John J. O’Shea
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News & Views |
Egocentric pre–T–cell receptors
The T-cell receptor on the surface of T cells requires antigen recognition to function. Structural studies reveal that its predecessor, the pre-T-cell receptor, is much more independent. See Letter p.844
- Bernard Malissen
- & Hervé Luche
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Letter |
The structural basis for autonomous dimerization of the pre-T-cell antigen receptor
The pre-T-cell antigen receptor mediates early T-cell development and differentiation. These authors report its structure and explain how the head-to-tail dimeric arrangement allows the interaction of the pre-Tα domain with any variable β domain, and provides the basis for ligand-independent signalling.
- Siew Siew Pang
- , Richard Berry
- & Jamie Rossjohn
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Letter |
Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance
Immune cells that recognize 'self' tissues need to be eliminated or controlled in order to prevent autoimmune diseases. Here, a T-cell population is delineated that is necessary to maintain self tolerance in mice. Genetic disruption of the inhibitory interaction between these CD8+ T cells and their target Qa-1+ follicular T-helper cells results in a lethal systemic-lupus-erythematosus-like autoimmune disease.
- Hye-Jung Kim
- , Bert Verbinnen
- & Harvey Cantor
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Outlook |
Dancing with an escape artist
Sarah DeWeerdt describes the intricate relationship between HIV and the host immune system, each influencing the other's next moves.
- Sarah DeWeerdt