Featured
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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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Outlook |
Asthma: Breathing new life into research
Asthma was once thought to be a uniform disease triggered by one type of immune cell. Researchers are now revealing the complexity of the condition and hope to hasten new drugs for forms unresponsive to steroids.
- Amy Maxmen
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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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Letter |
Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules
- Christine Moussion
- & Jean-Philippe Girard
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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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Letter |
HIV-1 adaptation to NK-cell-mediated immune pressure
- Galit Alter
- , David Heckerman
- & Marcus Altfeld
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Letter |
Oxysterols direct B-cell migration through EBI2
- Changlu Liu
- , Xia V. Yang
- & Timothy W. Lovenberg
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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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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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Letter |
Functional complementation between FADD and RIP1 in embryos and lymphocytes
Double deficiency of FADD and RIPK1 is shown to rescue the defects in mouse embryonic development and lymphocyte proliferation that are characteristic for mice with single gene deficiencies. This work suggests that the activity of FADD (presumably in conjunction with caspase-8 and c-FLIP) is to keep necrosis in check by causing the cleavage of RIPK1.
- Haibing Zhang
- , Xiaohui Zhou
- & Jianke Zhang
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Letter |
ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks
Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.
- Shan Zha
- , Chunguang Guo
- & Frederick W. Alt
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Letter |
H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes
Antigen receptor loci contain numerous gene segments that are recombined in response to antigen stimulation. The RAG endonuclease makes the double-strand breaks that initiate recombination. The ends of these breaks are hairpins that can only be cleaved by the Artemis nuclease. Here, it is shown that the specificity for Artemis is dictated by the histone protein H2AX, in cooperation with the repair protein MDC-1. In the absence of H2AX, another nuclease, CtIP, can open the ends but they are not joined efficiently; this leads to genomic instability.
- Beth A. Helmink
- , Anthony T. Tubbs
- & Barry P. Sleckman
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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 |
The structural basis for membrane binding and pore formation by lymphocyte perforin
Natural killer cells and cytotoxic T cells kill virus-infected and malignant cells, releasing the pore-forming protein perforin in the process. Perforin is required for the delivery of pro-apoptotic granzymes to the target cell. These authors present the crystal structure of a perforin monomer together with a cryo-electron microscopy reconstruction of the oligomeric pore. Perforin monomers within the pore are arranged with an inside-out orientation relative to the structurally homologous monomers of cholesterol-dependent cytolysins.
- Ruby H. P. Law
- , Natalya Lukoyanova
- & James C. Whisstock
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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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Research Highlights |
Immunology: Killer cells help
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Research Highlights |
Cardiovascular biology: Low B cells, low plaques
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News |
Well-trained immune cells keep HIV in check
Differences in T-cell development may explain why some infected people do not develop AIDS.
- Alla Katsnelson
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News & Views |
Close encounters of the second type
To combat intestinal worms, mammals rely on adaptive immune responses mediated by T cells. However, it seems that, initially, innate immune cells mimic T-cell activity, while T cells get ready for action.
- Gérard Eberl
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Letter |
IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses
Several non-haematopoietic-cell-derived cytokines, including interleukin (IL)25, have been implicated in inducing T helper 2 (TH2) cell-dependent inflammation, but their precise role has been unclear. Here, IL25 is shown to promote the accumulation of multipotent progenitor cells in gut-associated lymphoid tissue. These cells can give rise to macrophage or granulocyte lineages that promote the differentiation of TH2 cells and contribute to protective immunity against helminth infections.
- Steven A. Saenz
- , Mark C. Siracusa
- & David Artis
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Letter |
IκBζ regulates TH17 development by cooperating with ROR nuclear receptors
Interleukin-17-producing helper T (TH17) cells are a distinct T-cell subset characterized by its role in autoimmune disease. Here it is shown that the development of TH17 cells requires the transcription factor IκBζ, as well as nuclear receptors of the ROR family. Mice lacking IκBζ have a defect in TH17 development and are resistant to the induction of experimental autoimmune encephalomyelitis. The study points to some new potential molecular targets for drugs to treat autoimmune disease.
- Kazuo Okamoto
- , Yoshiko Iwai
- & Hiroshi Takayanagi
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Letter |
The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness
Quantification of the interaction of T-cell receptors with their peptide–MHC ligands in two–dimensional membranes is shown to yield larger dissociation rate constants than previous assays where one of the interacting partners was in solution.
- Jun Huang
- , Veronika I. Zarnitsyna
- & Cheng Zhu
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Letter |
B-cell-derived lymphotoxin promotes castration-resistant prostate cancer
In a mouse model of prostate cancer it is shown that infiltrating B cells promote tumorigenesis by secreting lymphotoxin. Lymphotoxin accelerates the emergence of castration-resistant prostate tumours in this model. Interfering with this pathway may offer therapeutic strategies for androgen-independent prostate cancer.
- Massimo Ammirante
- , Jun-Li Luo
- & Michael Karin
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News & Views |
The expanding TH2 universe
TH2 growth factors, which are involved in allergy and in defence against parasites, are produced by many different cell types, including a newly identified population found in fat-associated lymph clusters in the abdomen.
- Warren Strober
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Letter |
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
Immune homeostasis relies on tight control over the size of a population of regulatory T cells (Treg) that can suppress over-exuberant immune responses. Cells commit to the Treg lineage by upregulating the transcription factor Foxp3. Conserved non-coding DNA sequence elements at the Foxp3 locus are now shown to control the composition, size and maintenance of the Treg cell population.
- Ye Zheng
- , Steven Josefowicz
- & Alexander Y. Rudensky