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| Open AccessAutoreactive T cells target peripheral nerves in Guillain–Barré syndrome
Autoreactive T cells that target myelin antigens in the peripheral nerves are present in patients with the demyelinating form of Guillain–Barré syndrome, and these T cells are likely to contribute to disease pathophysiology.
- L. Súkeníková
- , A. Mallone
- & D. Latorre
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Article
| Open AccessSingle-cell CRISPR screens in vivo map T cell fate regulomes in cancer
Analyses of causal gene regulatory networks have identified key checkpoints mediating the progressive differentiation of CD8+ cytotoxic T cells, findings that have implications for anticancer immunotherapies such as adoptive cell therapy and immune checkpoint blockade.
- Peipei Zhou
- , Hao Shi
- & Hongbo Chi
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Reductive carboxylation epigenetically instructs T cell differentiation
Reductive carboxylation of glutamine by isocitrate dehydrogenase 2 (IDH2) has a role in determining the fate of T cells, and inhibiting this enzyme promotes the differentiation of memory T cells.
- Alison Jaccard
- , Tania Wyss
- & Mathias Wenes
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The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Stress-associated catecholamines promote CD8+ T cell exhaustion through the β1-adrenergic receptor, and blocking β-adrenergic signalling may help restore anti-tumour functions.
- Anna-Maria Globig
- , Steven Zhao
- & Susan M. Kaech
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CRISPR screens decode cancer cell pathways that trigger γδ T cell detection
A combination of genome-wide CRISPR screens in target cancer cells identifies pathways that regulate γδ T cell killing and BTN3A cell surface expression.
- Murad R. Mamedov
- , Shane Vedova
- & Alexander Marson
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Article
| Open AccessA common allele of HLA is associated with asymptomatic SARS-CoV-2 infection
The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.
- Danillo G. Augusto
- , Lawton D. Murdolo
- & Jill A. Hollenbach
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Article
| Open AccessMicrobial peptides activate tumour-infiltrating lymphocytes in glioblastoma
Tumour-infiltrating lymphocytes from glioblastoma can recognize bacterial and gut microbial peptides.
- Reza Naghavian
- , Wolfgang Faigle
- & Roland Martin
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Article |
The NK cell receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells
NKp46 recognizes externalized calreticulin, which translocates from the ER to the cell membrane during ER stress, indicating a danger-associated molecular pattern that eliminates ER-stressed cells.
- Sumit Sen Santara
- , Dian-Jang Lee
- & Judy Lieberman
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SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.
- Wafaa B. Alsoussi
- , Sameer Kumar Malladi
- & Ali H. Ellebedy
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Matters Arising |
GOT1 constrains TH17 cell differentiation, while promoting iTreg cell differentiation
- Wei Xu
- , Chirag H. Patel
- & Jonathan D. Powell
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Article
| Open Accessγδ T cells are effectors of immunotherapy in cancers with HLA class I defects
γδ T cells contribute to the response to immune checkpoint blockade treatment in patients with HLA-class-I-negative DNA mismatch repair-deficient colon cancers. .
- Natasja L. de Vries
- , Joris van de Haar
- & Emile E. Voest
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Article
| Open AccessFunctional antibodies exhibit light chain coherence
Among naturally occurring antibodies that have adapted to antigen, those with similar heavy chains usually have similar light chains.
- David B. Jaffe
- , Payam Shahi
- & Wyatt J. McDonnell
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PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program
PD-1+TCF1+ stem-like CD8+ T cells—precursors of exhausted CD8+ T cells—are not fate-locked into the exhaustion program; their differentiation trajectory can be changed by IL-2 signals.
- Masao Hashimoto
- , Koichi Araki
- & Rafi Ahmed
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Immune tolerance of food is mediated by layers of CD4+ T cell dysfunction
Immune tolerance to food is mediated by CD4+ T cells forming subsets of T helper cells lacking the capacity to trigger gut pathology but able to produce regulatory T cells that may suppress it.
- Sung-Wook Hong
- , Peter D. Krueger
- & Marc K. Jenkins
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cBAF complex components and MYC cooperate early in CD8+ T cell fate
cBAF is a negative determinant of memory T cell fate and the manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.
- Ao Guo
- , Hongling Huang
- & Douglas R. Green
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Single-cell eQTL models reveal dynamic T cell state dependence of disease loci
A single-cell Poisson model is used to analyse eQTLs in memory T cells across continuous, dynamic cell states, revealing that the cell context is critical to understanding variation in eQTLs and their association with disease.
- Aparna Nathan
- , Samira Asgari
- & Soumya Raychaudhuri
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Landscape of helper and regulatory antitumour CD4+ T cells in melanoma
A survey of the CD4+ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.
- Giacomo Oliveira
- , Kari Stromhaug
- & Catherine J. Wu
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Programme of self-reactive innate-like T cell-mediated cancer immunity
A survey of T cell populations in human and mouse tumours identifies a population of cancer-sensing IL-15-activated αβ T cell receptor-positive FCER1G-expressing innate-like T cells with high cytotoxic potential.
- Chun Chou
- , Xian Zhang
- & Ming O. Li
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A genome-scale screen for synthetic drivers of T cell proliferation
A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.
- Mateusz Legut
- , Zoran Gajic
- & Neville E. Sanjana
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Establishment of fetomaternal tolerance through glycan-mediated B cell suppression
Pathways of glycan-mediated B cell suppression during pregnancy are important for promoting fetomaternal tolerance.
- G. Rizzuto
- , J. F. Brooks
- & A. Erlebacher
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Article |
Germinal centre-driven maturation of B cell response to mRNA vaccination
Sequencing of B cell receptors and expression of the corresponding monoclonal antibodies is used to characterize the evolution of the long-term B cell response to SARS-CoV-2 mRNA vaccination.
- Wooseob Kim
- , Julian Q. Zhou
- & Ali H. Ellebedy
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Article
| Open AccessVaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron
Current vaccines induce broadly cross-reactive cellular immunity against SARS-CoV-2 variants, including Omicron, and provide protection against severe disease despite a substantially reduced neutralizing antibody response.
- Jinyan Liu
- , Abishek Chandrashekar
- & Dan H. Barouch
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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity
CRISPR screening and protein–protein interaction networks identify components and mechanisms of nutrient-dependent mTORC1 signalling in regulatory T cells and reveal how mTORC1 integrates immunological cues and nutrient signals for adaptive immunity.
- Lingyun Long
- , Jun Wei
- & Hongbo Chi
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Article
| Open AccessPre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.
- Leo Swadling
- , Mariana O. Diniz
- & Mala K. Maini
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Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin
Time-limited skin inflammation in neonatal mice promotes a reciprocal interaction between type 2 helper T cells and fascial fibroblasts that regulates wound repair in later life.
- Ian C. Boothby
- , Maxime J. Kinet
- & Michael D. Rosenblum
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Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer
An analysis of human papillomavirus (HPV)-specific CD8 T cells in patients with head and neck cancer identifies functional PD-1+TCF-1+CD8 T cells in the tumour with implications for therapeutic vaccination and PD-1 directed immunotherapy.
- Christiane S. Eberhardt
- , Haydn T. Kissick
- & Rafi Ahmed
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Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma
The authors use single-cell profiling and T cell receptor specificity screening to show how tumour antigen recognition shapes the phenotypes of CD8+ T cells and antitumour immune responses.
- Giacomo Oliveira
- , Kari Stromhaug
- & Catherine J. Wu
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Article
| Open AccessTranscriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers
Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade.
- Justina X. Caushi
- , Jiajia Zhang
- & Kellie N. Smith
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Review Article |
A multilayered immune system through the lens of unconventional T cells
This Review provides an overview of our current understanding of the unconventional T cell compartment and discusses the development and function of unconventional T cells from an evolutionary perspective.
- Toufic Mayassi
- , Luis B. Barreiro
- & Bana Jabri
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Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine
Enzymes in the cytidine diphosphate–ethanolamine metabolic pathway, which promotes de novo synthesis of phosphatidylethanolamine, are shown to act as post-transcriptional mediators of the differentiation of T follicular helper (TFH) cells, by regulating the chemokine receptor CXCR5.
- Guotong Fu
- , Clifford S. Guy
- & Hongbo Chi
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SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Analysis of antigen-specific B cells in lymph nodes of individuals vaccinated with BNT162b2 reveals lasting germinal centre responses, explaining the robust humoral immunity induced by SARS-CoV-2 mRNA-based vaccines.
- Jackson S. Turner
- , Jane A. O’Halloran
- & Ali H. Ellebedy
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SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans
SARS-CoV-2 infection induces long-lived bone marrow plasma cells that correlate with anti-SARS-CoV-2 spike protein antibody titres in individuals who have recovered from COVID-19.
- Jackson S. Turner
- , Wooseob Kim
- & Ali H. Ellebedy
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Expansible residence decentralizes immune homeostasis
Investigations in mice using parabiosis and cohousing experiments reveal that nonlymphoid organs serve as reservoirs of tissue-autonomous cellular immunity, leading to the decentralization of organism-level immune homeostasis.
- Sathi Wijeyesinghe
- , Lalit K. Beura
- & David Masopust
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Lipid signalling enforces functional specialization of Treg cells in tumours
Identification of a metabolic checkpoint involving lipid signalling that is specific to regulatory T cells (Treg cells) in the tumour microenvironment raises the possibility of targeting this checkpoint for treatment of cancer.
- Seon Ah Lim
- , Jun Wei
- & Hongbo Chi
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Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
The tumour microenvironment is low in glucose and high in the alternative metabolite lactate, which regulatory T cells are shown here to use, maintaining their ability to suppress effector immune cells.
- McLane J. Watson
- , Paolo D. A. Vignali
- & Greg M. Delgoffe
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Dynamic regulation of TFH selection during the germinal centre reaction
T follicular helper cells undergo antigen-dependent selection in germinal centres, with higher-affinity T cell receptors supporting stronger proliferation leading to their clonal dominance.
- Julia Merkenschlager
- , Shlomo Finkin
- & Michel C. Nussenzweig
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Article |
Loop extrusion mediates physiological Igh locus contraction for RAG scanning
Long-distance V(D)J recombination is facilitated by contraction of the Igh locus and linear RAG scanning along chromatin, both driven by cohesin-mediated loop extrusion, which allows recombination of widely separated gene segments to occur.
- Hai-Qiang Dai
- , Hongli Hu
- & Frederick W. Alt
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Article |
Defining HPV-specific B cell responses in patients with head and neck cancer
Detailed analyses of B cells in the tumour microenvironment of human papilloma virus (HPV)-linked head and neck cancers reveal strong humoral immune responses to HPV antigens and the secretion of HPV-specific antibodies in situ.
- Andreas Wieland
- , Mihir R. Patel
- & Rafi Ahmed
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IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
IFITM3 shifts upon phosphorylation from acting as an antiviral effector to being a scaffold for PIP3 and thereby amplifies PI3K signalling, which can be co-opted for malignant transformation in B cell leukaemia and lymphoma.
- Jaewoong Lee
- , Mark E. Robinson
- & Markus Müschen
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Human germinal centres engage memory and naive B cells after influenza vaccination
The human germinal centre response to influenza virus vaccination is fuelled by the continued recruitment of naive B cells as well as pre-existing memory B cells.
- Jackson S. Turner
- , Julian Q. Zhou
- & Ali H. Ellebedy
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CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning
Using an auxin-inducible approach, the authors show that downmodulation of CTCF activity promotes cohesin-driven RAG endonuclease scanning, and thus V(D)J recombination, across the Igh locus.
- Zhaoqing Ba
- , Jiangman Lou
- & Frederick W. Alt
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Wapl repression by Pax5 promotes V gene recombination by Igh loop extrusion
Pax5 regulates contraction of the immunoglobulin heavy chain (Igh) locus—an essential step in V(D)J recombination—by promoting chromatin loop extrusion via repression of Wapl expression.
- Louisa Hill
- , Anja Ebert
- & Meinrad Busslinger
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Gasdermin E suppresses tumour growth by activating anti-tumour immunity
The gasdermin E protein is shown to act as a tumour suppressor: it is cleaved by caspase 3 and granzyme B and leads to pyroptosis of cancer cells, provoking an immune response to the tumour.
- Zhibin Zhang
- , Ying Zhang
- & Judy Lieberman
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γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
Vγ6+ Vδ1+ γδ T cells control tolerance to cold by activating adipocyte IL-17RC and promoting sympathetic innervation of thermogenic adipose tissue in mice.
- Bo Hu
- , Chengcheng Jin
- & Bruce M. Spiegelman
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Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells
The interleukin-15 superagonist N-803, combined with the depletion of CD8+ lymphocytes, induced a robust and persistent reactivation of the virus in vivo in both antiretroviral-therapy-treated SIV-infected macaques and HIV-infected humanized mice.
- Julia Bergild McBrien
- , Maud Mavigner
- & Guido Silvestri
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An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
The authors examine the immune cell infiltrates of human tumours and provide evidence for a population of CD8 T cells with stem-cell characteristics and proliferative capacity that reside in an antigen-presenting niche within tumours.
- Caroline S. Jansen
- , Nataliya Prokhnevska
- & Haydn Kissick
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Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy
CRISPR–Cas9 mutagenesis screenings reveal that targeting REGNASE-1 leads to improved therapeutic efficacy of CD8+ T cells against mouse models of cancer, and identify BATF as a key target of REGNASE-1.
- Jun Wei
- , Lingyun Long
- & Hongbo Chi
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VISTA is an acidic pH-selective ligand for PSGL-1
V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.
- Robert J. Johnston
- , Linhui Julie Su
- & Alan J. Korman
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Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
CD8+ T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.
- Alexandre P. Bénéchet
- , Giorgia De Simone
- & Matteo Iannacone