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| Open AccessFollicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
T follicular regulatory cells control the magnitude of the germinal centre response. Here the authors show that these cells display specificity to self as well as foreign antigens, and can arise from Foxp3-negative precursors at early stages of immunization in a PD-L1 dependent manner.
- Meryem Aloulou
- , Edward J. Carr
- & Michelle A. Linterman
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Article
| Open AccessSystematic pan-cancer analysis of tumour purity
The importance of the tumour microenvironment has now been realised, however the presence of non-tumour cells in cancer samples can complicate genomic analyses. Here, the authors estimate tumour purity in 10,000 samples from the TCGA dataset and can detect a signature of T cell activation.
- Dvir Aran
- , Marina Sirota
- & Atul J. Butte
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| Open AccessDose–response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies
Potencies of HIV broadly neutralizing antibodies are usually defined by theirin vitro IC50 and IC80 values, but much higher levels will be required for successful immunotherapies. Here, Webb et al. predict antibody potency at therapeutic levels by analyzing dose–response curve slopes, which correlate with epitope class.
- Nicholas E. Webb
- , David C. Montefiori
- & Benhur Lee
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| Open AccessFunctional classification of memory CD8+ T cells by CX3CR1 expression
The function of memory CD8+ T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8+T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.
- Jan P. Böttcher
- , Marc Beyer
- & Percy A. Knolle
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| Open AccessBreaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer’s disease pathology
Immunosuppression has been unsuccessful in treatment of Alzheimer’s disease. Here the authors show in a mouse model of the disease that transient inhibition of regulatory T cells mitigates amyloid plaque pathology and reverses cognitive decline, whereas augmenting these cells worsens the pathology.
- Kuti Baruch
- , Neta Rosenzweig
- & Michal Schwartz
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Article
| Open AccessIL10-driven STAT3 signalling in senescent macrophages promotes pathological eye angiogenesis
Pathological neovascularization causes blinding eye disease. Here the authors show that IL10 activates STAT3 signalling in the macrophages in the ageing eye, promoting their polarization towards a pro-angiogenic phenotype; interfering with this pathway reverses the pathology in a mouse model.
- Rei Nakamura
- , Abdoulaye Sene
- & Rajendra S. Apte
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Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus
Treatment options for prevention and control of fatal H7N9 influenza infections remain limited. Here, the authors show that two human monoclonal antibodies protect mice against H7N9 strains when administered before or after H7N9 infection.
- Zhe Chen
- , Jianmin Wang
- & Qi Jin
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Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells
The need to develop vaccines against pathogens such as HIV requires the development of strategies to overcome inhibitory immunoregulatory mechanisms. Here, the authors report that murine natural killer cells inhibit CD4- and follicular helper T cells, leading to a weaker germinal center response and diminished virus-specific immune memory.
- Carolyn Rydyznski
- , Keith A. Daniels
- & Stephen N. Waggoner
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An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction
Tim-3 is an inhibitory molecule that suppresses T-cell responses. Here the authors show that the cytokine IL-27, acting through the transcription factor NFIL3, induces Tim-3 in vivo, and that IL-27-conditioned Th1 cells have poor effector function.
- Chen Zhu
- , Kaori Sakuishi
- & Vijay K. Kuchroo
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Article
| Open AccessGlucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M
Glucocorticoids strongly suppress inflammation. Here the authors show that this suppression is mediated by induction of the negative inflammatory regulator IRAK-M, and demonstrate its important role in host defense against the pneumonia-causative bacterium, non-typeable Haemophilus influenzae.
- Masanori Miyata
- , Ji-Yun Lee
- & Jian-Dong Li
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Article
| Open AccessSequential transcriptional changes dictate safe and effective antigen-specific immunotherapy
Dose escalation in antigen-specific therapies is recognized as safe and effective, but the underlying effects of dosing variables on the immune system are not understood. Here, the authors demonstrate that dose escalation causes sequential modulation of gene expression among antigen-specific lymphocytes.
- Bronwen R. Burton
- , Graham J. Britton
- & David C. Wraith
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Article
| Open AccessProtective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Induction of protective immunity mediated by CD8+ T cells has been a long sought goal in vaccinology. Here, Ewer et al. report induction of protective efficacy against Plasmodium falciparummalaria in a phase IIa prime-boost vaccine trial where efficacy correlates strongly with induced CD8 T-cell responses.
- Katie J. Ewer
- , Geraldine A. O’Hara
- & Adrian V. S. Hill
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High doses of CpG oligodeoxynucleotides stimulate a tolerogenic TLR9–TRIF pathway
CpG oligodeoxynucleotides stimulate innate immune signalling and are of significant interest as therapeutics. Here the authors show that at high doses, these molecules induce an opposite, tolerogenic effect, acting through a previously uncharacterized Toll-like receptor-dependent pathway.
- Claudia Volpi
- , Francesca Fallarino
- & Paolo Puccetti
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CD91-dependent programming of T-helper cell responses following heat shock protein immunization
Heat shock proteins bind to CD91 on antigen presenting cells, resulting in the presentation of chaperoned peptides to T cells. Here, heat shock protein binding is shown to induce phosphorylation of CD91 and stimulate the production of cytokines, thus priming various T-helper cell responses.
- Sudesh Pawaria
- & Robert J. Binder
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| Open AccessPandemic 2009 H1N1 vaccine protects against 1918 Spanish influenza virus
Vaccination against one viral strain can result in cross-reactive antibodies against another viral strain. In this study, the vaccination of mice against the 2009 H1N1 virus is shown to protect mice from the 1918 Spanish influenza virus, which resulted in millions of deaths worldwide.
- Rafael A. Medina
- , Balaji Manicassamy
- & Adolfo García-Sastre