Featured
-
-
Article
| Open AccessAntigen presentation by B cells enables epitope spreading across an MHC barrier
Increasing evidence suggests that antigen presentation by B cells is critical to the initiation of autoimmunity. Here, the authors demonstrate that tolerance breakdown is initiated outside of germinal centres and that B cells can directly instruct T cells to break tolerance and propagate autoimmune responses.
- Cecilia Fahlquist-Hagert
- , Thomas R. Wittenborn
- & Søren E. Degn
-
Article
| Open AccessMitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming
Exhaustion is the functional deterioration of T cells following chronic stimulation. Here, Wu et al. show that mitochondrial dysfunction drives T cell exhaustion by inhibiting HIF-1α degradation and transcriptional metabolic reprogramming.
- Hao Wu
- , Xiufeng Zhao
- & Martin Vaeth
-
Article
| Open AccessRespiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
Evidence from animal models suggest a vital role for mucosal vaccination in inducing protection from coronavirus infection. Here the authors examine the B and T cell responses at the lower airways, and contrast humoral and cellular immunity of people after infection and vaccination.
- Elena Mitsi
- , Mariana O. Diniz
- & Daniela M. Ferreira
-
Article
| Open AccessImmune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells
CD4+ T cells have been shown to be important in CD8+ T cell responses through a process of DC:T cell interaction. Here the authors further characterise this DC:T cell interaction and show that after CD4+ T cell help these post-synaptic DCs have increased lipid peroxidation and increased MHC class I proteins associated with increased cross-presentation function.
- Diego Calzada-Fraile
- , Salvador Iborra
- & Francisco Sánchez-Madrid
-
Article
| Open AccessSARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors
Although SARS-CoV2 epitope characterization has been the focus of extensive research, these efforts have largely focused on the spike protein. Here, the authors demonstrate that CD8+ T cell responses can be directed against a dominant nucleocapsid epitope and rely on a highly focused T cell receptor repertoire.
- Cecily Choy
- , Joseph Chen
- & Nan-Ping Weng
-
Article
| Open AccessSIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions
Here, the authors used cryo-EM to explore secretory Immunoglobulin A interactions with bacterial and host receptors, uncovering unexpected binding stoichiometry and unappreciated functional consequences relevant to understanding host-pathogen interactions.
- Qianqiao Liu
- & Beth M. Stadtmueller
-
Article
| Open AccessInterferon-γ couples CD8+ T cell avidity and differentiation during infection
Although IFN-γ is known to regulate T cell function and expansion during virus-specific responses, its impact on T cells with varying avidity for antigen remains unclear. Here, the authors demonstrate that IFN-γ promotes the expansion of low-avidity CD8+ T cells during the effector phase, but favours those with high avidity in the memory pool.
- Lion F. K. Uhl
- , Han Cai
- & Audrey Gerard
-
Article
| Open AccessActivation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination
Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.
- Malika Aid
- , Kathryn E. Stephenson
- & Dan H. Barouch
-
Article
| Open AccessThe transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells
Type 1 conventional dendritic cells (cDC1) play a pivotal role in the cross-presentation of antigens, enabling efficient CD8 + T cell response. Here authors show that the transcription factor Zeb1 essentially regulates this process via facilitating the reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytoplasm.
- Yan Wang
- , Quan Zhang
- & Nengming Xiao
-
Article
| Open AccessA spatial sequencing atlas of age-induced changes in the lung during influenza infection
Ageing is known to impair the immune response against infectious pathogens. Here, Kasmani et al. present a spatial and transcriptomic atlas of immune changes in the lungs of young and aged mice in response to influenza virus infection.
- Moujtaba Y. Kasmani
- , Paytsar Topchyan
- & Weiguo Cui
-
Article
| Open AccessComprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
Neutralizing antibodies are key to resolving viral infections and confer long-term protection. This work provides a detailed analysis of how murine and human sera neutralize a non-enveloped human virus, coxsackievirus B3, and how the virus can escape them.
- Beatriz Álvarez-Rodríguez
- , Javier Buceta
- & Ron Geller
-
Article
| Open AccessHIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria
HIV-1 infection is known to impact the gut mucosa, effecting the microbiota and immune system, but early antiretroviral therapy is linked to partial reversal of this phenomena. Here the authors explore the impact of early commencement of antiretroviral therapy and show this can limit the abnormal responses of intestinal B cells associated with HIV-1 infection.
- Cyril Planchais
- , Luis M. Molinos-Albert
- & Hugo Mouquet
-
Article
| Open AccessViral kinetics of sequential SARS-CoV-2 infections
In this study, the authors compare the viral kinetics of first and second SARS-CoV-2 infections using data from an occupational surveillance scheme in the National Basketball League. They find that second infections tend to have a faster clearance time, and that clearance times in first and second infections were positively correlated.
- Stephen M. Kissler
- , James A. Hay
- & Yonatan H. Grad
-
Article
| Open AccessPrevious infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2
Here, the authors analysed immune response to two consecutive coronavirus infections and observed that hamsters infected with seasonal coronaviruses were not protected from COVID-19 despite cross-reactive antibodies. Antiviral and germinal center B cell responses were suppressed but not during SARS-CoV-2 variant infections.
- Magen E. Francis
- , Ethan B. Jansen
- & Alyson A. Kelvin
-
Article
| Open AccessTracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration
Skin scarring devoid of dermal appendages has unfavorable effects on aesthetic and physiological functions. Here, the authors present a treatment based on extracellular matrix scaffolds and perform multimodal analysis to highlight the role of Tregs recruited by the biomaterial in mitigating tissue fibrous by suppressing excessive inflammation.
- Yang Yang
- , Chenyu Chu
- & Yili Qu
-
Article
| Open AccessDefining a TCF1-expressing progenitor allogeneic CD8+ T cell subset in acute graft-versus-host disease
Graft-versus-host disease (GvHD) is mediated by activated T cells. Here the authors study mouse models of allogeneic and xenogeneic GvHD, and define T cell factor-1 (TCF1)+ and TCF1- T cell subsets with distinct functions and differentiation pathways that participate in GvHD pathogenesis.
- Solhwi Lee
- , Kunhee Lee
- & Se Jin Im
-
Article
| Open AccessLarge T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.
- Cirino Botta
- , Cristina Perez
- & Bruno Paiva
-
Article
| Open AccessGerminal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells
Loss-of-function mutations in the chromatin remodelling protein HELLS result in humoral immune deficiency. Authors here show in a conditional knockout mouse model that HELLS controls the kinetics of a typical germinal center response by DNA methylation, its absence leading to either the appearance of memory-B cell markers or a metabolic state change typical of plasma cells.
- Clara Cousu
- , Eléonore Mulot
- & Sébastien Storck
-
Article
| Open AccessHMGB2 regulates the differentiation and stemness of exhausted CD8+ T cells during chronic viral infection and cancer
T cells can become exhausted during chronic virus infection or repeated stimulation by tumour antigens. Here the authors show that High-Mobility Group Box 2 (HMGB2) protein promotes CD8+ T cell memory cell generation in acute viral infection and exhaustion stemness in chronic infection.
- Emily N. Neubert
- , Julia M. DeRogatis
- & Roberto Tinoco
-
Article
| Open AccessLet-7 enhances murine anti-tumor CD8 T cell responses by promoting memory and antagonizing terminal differentiation
Effective CD8+ T cell immunity requires the generation of a long-lived memory pool and the maintenance of a non-exhausted effector T cell pool. The implementation of immune checkpoint blockade can reduced levels of exhaustion but lacks the ability to support memory formation in the effector pool. Here the authors suggest a role for Let-7 in the enhancement of the anti-tumor CD8+ T cell response by supporting memory via modulation of metabolic and differentiation state.
- Alexandria C. Wells
- , Kaito A. Hioki
- & Leonid A. Pobezinsky
-
Article
| Open AccessEngaging an HIV vaccine target through the acquisition of low B cell affinity
Broadly neutralizing antibodies (bnAbs) for HIV have been difficult to elicit with one issue being the low B cell affinity required. Here the authors use a transgenic mouse bearing human-like antibody repertoires to show that low affinity B cells persist which enables vaccine expansion of antibodies against the CD4 binding site, a conserved HIV bnAb target.
- Larance Ronsard
- , Ashraf S. Yousif
- & Daniel Lingwood
-
Article
| Open AccessAcquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
Acquired resistance to immune checkpoint inhibitors limits therapeutic success in non-small-cell lung cancer, however, the underpinning immune parameters are largely unknown. Here authors distinguish resistance types based on immune cell infiltration, immune checkpoint molecule and cytokine expression level, using paired samples from patients in the sensitive and in the resistant disease phase.
- Stefanie Hiltbrunner
- , Lena Cords
- & Alessandra Curioni-Fontecedro
-
Article
| Open AccessDownregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development
Peripheral CD4+ T cells can develop into Intestinal intraepithelial lymphocytes (IEL) in the lamina propria. Here the authors characterise how IEL generation from CD4+ T cells is regulated and show using scRNA sequencing that Ccr9 is involved in this process through limiting IEL precursor differentiation.
- Keiko Ono
- , Tomohisa Sujino
- & Takanori Kanai
-
Article
| Open AccessSARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations
As the SARS-SoV-2 pandemic progressed and the vaccinated population increased, a number of variants of concerns that circumvented the vaccine induced immunity emerged. Here the authors compare SARS-SoV-2 mRNA vaccine responses in pregnant women and other people, characterising the antibody response and Fc functions, and potency against a range of variants of concern.
- Andrew P. Hederman
- , Harini Natarajan
- & Margaret E. Ackerman
-
Article
| Open AccessAntibody-mediated NK cell activation as a correlate of immunity against influenza infection
Antibodies play a crucial role in protection from influenza virus infection, but functional details, particularly in older adults, are incomplete. Here the authors show that NK cell-activating antibodies are associated with protection from influenza infection in vaccinated older adults.
- Carolyn M. Boudreau
- , John S. Burke IV
- & Galit Alter
-
Article
| Open AccessAn integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells
B cells pursue specific genetic programs to facilitate downstream cellular functions. Here the authors identify, using a combination of proteomic, transcriptomic and functional analyses, a group of mRNAs related to early activation and antibody production that are expressed in B cells without corresponding proteins, hinting a ‘poised’ state of B cells.
- Fiamma Salerno
- , Andrew J. M. Howden
- & Martin Turner
-
Article
| Open AccessOmicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
The authors characterize immune response in Omicron-infected vaccinated individuals and observe an immune enhancement. While increases in neutralizing antibodies and spike T cells are stronger in previously naïve individuals, mucosal antibodies and non-spike responses increase regardless of infection history.
- Hailey Hornsby
- , Alexander R. Nicols
- & Thushan I. de Silva
-
Article
| Open AccessElevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers
Data on antibody response to SARS-CoV-2 in infants directly compared with their mothers is limited. Stoddard et al. find distinct antibody profiles in infants, including elevated levels of antibody binding to Spike, elevated ADCC, and convergent antibody binding escape profiles in the Spike fusion peptide.
- Caitlin I. Stoddard
- , Kevin Sung
- & Julie Overbaugh
-
Article
| Open AccessA single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia
Achalasia is a rare motility disorder of the esophagus resulting from abnormal immune responses, but the immunologic mechanism is unclear. Here the authors use scRNA-seq of PBMC and esophageal lower sphincter tissue and find C1QC+ macrophages and tissue-resident memory T cells with expanded compositions and altered transcriptional profiles in achalasia.
- Zu-Qiang Liu
- , Hao Dai
- & Quan-Lin Li
-
Article
| Open AccessCorrelates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2
Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.
- Tomer Hertz
- , Shlomia Levy
- & Orly Weinstein
-
Article
| Open AccessMonoclonal antibody levels and protection from COVID-19
Monoclonal antibodies (mAbs) have shown efficacy against SARS-CoV-2 infection in clinical trials. Here the authors model the dose-response relationship between the dose of mAbs and protection from symptomatic SARS-CoV-2 infection. Further, the protection is comparable to that achieved by vaccination.
- Eva Stadler
- , Martin T. Burgess
- & David S. Khoury
-
Article
| Open AccessA highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
Rift valley fever virus (RVFV) infection during pregnancy has been associated with late-term fetal loss. Here, the authors show that a neutralizing monoclonal antibody can prevent vertical transmission of RVFV when administered either pre- or post-infection in a rodent model.
- Cynthia M. McMillen
- , Nathaniel S. Chapman
- & Amy L. Hartman
-
Article
| Open AccessGenetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire
Haplotype diversity in the human immunoglobulin heavy chain (IGH) locus is poorly characterized. Here, the authors use long-read sequencing to discover extensive IGH diversity and link germline variants to variation in the antibody repertoire.
- Oscar L. Rodriguez
- , Yana Safonova
- & Corey T. Watson
-
Article
| Open AccessMolecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Nirsevimab binds the respiratory syncytial virus (RSV) fusion protein and has been tested for RSV prevention in clinical trials. Here, the authors analyse RSV from infections and show that binding site substitutions are rare and that over 99% of isolates remain susceptible to nirsevimab.
- Bahar Ahani
- , Kevin M. Tuffy
- & Tonya Villafana
-
Article
| Open AccessIKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection
CD8+ T resident memory (TRM) cells are important in protection against virus infection and NFκB signalling may function in this process. Here the authors use an inducible transgenic mouse models where T cell intrinsic NFκB levels can be increased or decreased which affects how CD8+ TRM cells seed into the lungs after influenza infection.
- Curtis J. Pritzl
- , Dezzarae Luera
- & Emma Teixeiro
-
Article
| Open AccessVγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males
Traumatic brain injury is not only a neurological but also an immunological condition in which multiple innate and adaptive immune cell types play roles. Here authors show in a mouse model that the Vγ4 subtype of the unconventional gamma-delta T cells promote neuroinflammation, while the Vγ1 subtype ameliorates immunopathology.
- Hadi Abou-El-Hassan
- , Rafael M. Rezende
- & Howard L. Weiner
-
Article
| Open AccessImmunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters
Long-term BA.5-specific efficiency of booster vaccination is incompletely understood. Here, analyzing immunity to and efficacy of various COVID-19 vaccination regimens in Syrian hamster, the authors found that heterologous boosting provides more durable immunity and that NVX-CoV2373 provides the strongest boosting effect.
- Rafael R. G. Machado
- , Jordyn L. Walker
- & Scott C. Weaver
-
Article
| Open AccessStructural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants
In this study, the authors isolated SARS-CoV-2 receptor binding site monoclonal antibodies resistant to Omicron mutations. An amino acid in the receptor binding domain, tyrosine-489, is a virus-vulnerable site and a common footprint of broadly neutralizing antibodies.
- Saya Moriyama
- , Yuki Anraku
- & Yoshimasa Takahashi
-
Article
| Open AccessWaning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination
Efficiency of SARS-CoV-2 vaccines has long been attributed to the neutralising capacity of the antibodies that are produced upon prime-boost vaccinations. Here authors show that upon vaccination with CoronaVac and BNT162b2 vaccines in prime-boost regimens, antibodies with Fc-effector functions to enhance cellular and innate immunity are also produced, albeit with different kinetics.
- X. Tong
- , R. P. McNamara
- & R. A. Medina
-
Article
| Open AccessToll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses
Compared to germinal centres, extrafollicular plasmablast responses are thought to produce lower affinity antibodies, offering little protection from infection. Here authors show in an influenza infection and immunization mouse model that extrafollicular responses could yield protective antibodies, and that their development depends on signals provided via Toll-like receptor stimulation.
- Jonathan H. Lam
- & Nicole Baumgarth
-
Article
| Open AccessT cell receptor signaling strength establishes the chemotactic properties of effector CD8+ T cells that control tissue-residency
CD8+ T cells are found within peripheral tissues including the skin. Here, the authors use an interferon-gamma reporter system and viruses expressing agonistic peptides of varying affinities to investigate how T cell receptor signaling strength changes the chemotactic properties of effector CD8+ T cells to promote tissue-residency.
- Mahmoud Abdelbary
- , Samuel J. Hobbs
- & Jeffrey C. Nolz
-
Article
| Open AccessDifferentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis
Interleukin 26 (IL-26) has been shown to have antimicrobial and pro-inflammatory effects. Here the authors establish a role for IL-26 in the generation of IL-17A producing Th17 CD4+ T cells and suggest it involves epithelial cross talk in skin lesions of psoriasis patients.
- Anissa Fries
- , Fanny Saidoune
- & Michel Gilliet
-
Article
| Open AccessImmunological imprinting of humoral immunity to SARS-CoV-2 in children
The immune responses to SARS CoV-2 infection in children are less well understood than in adults. Here the authors characterise immune responses to newer omicron lineages and relate these to previous infection with earlier lineages of SARS-CoV-2, implicating a reduced immunogenicity from omicron variants and imprinting from previous virus strains.
- Alexander C. Dowell
- , Tara Lancaster
- & Paul Moss
-
Article
| Open AccessAge-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade
Age-associated B cells (ABC) have been shown to be associated with autoimmunity and ageing. Here the authors examine whether ABC are transcriptionally or functionally altered in participants with reduced immune cell function and show that, being transcriptionally similar, high pre-vaccine levels are associated with poor vaccine response.
- Juan Carlos Yam-Puc
- , Zhaleh Hosseini
- & James E. D. Thaventhiran
-
Article
| Open AccessCampylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques
Utilising various Campylobacter vaccination regimens, the authors explore the effect of vaccination on Campylobacter-associated diarrhoea, mortality, and growth kinetics in vaccinated infant rhesus macaques.
- Sara M. Hendrickson
- , Archana Thomas
- & Mark K. Slifka
-
Article
| Open AccessUnmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses
Here the authors show that in non-human primates two doses of an mRNA-based rabies vaccine induce higher levels of vaccine-specific B cells and cross-neutralizing antibodies compared to two doses of a licensed whole inactivated virus vaccine.
- Fredrika Hellgren
- , Alberto Cagigi
- & Karin Loré
-
Article
| Open AccessNBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells
NBEAL2 loss of function mutations lead to grey platelet syndrome, a condition characterised by α-granule-deficient platelets and, in a proportion of cases, by autoimmunity. Here authors show that NBEAL2 physically interacts with CTLA-4 in human T cells, and NBEAL2 deficiency leads to reduced CTLA-4 surface expression in effector T cells, but not regulatory T cells, thus tipping the balance towards autoimmunity.
- Laure Delage
- , Francesco Carbone
- & Frédéric Rieux-Laucat
-
Article
| Open AccessExamining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration
Here the authors assess neutralizing antibody (nAb) levels as correlate of protection in a monoclonal antibody prevention trial and a vaccine trial for COVID-19 and show that nAb titers correlate with clinical protection against COVID-19 supporting nAb titer as a surrogate endpoint for authorization of monoclonal antibodies.
- Dean Follmann
- , Meagan P. O’Brien
- & Myron S. Cohen
-
Article
| Open AccessSpatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4+ T cell fate
It is debated how follicular helper T (Tfh) cells versus central memory CD4+ T cells arise from similar precursors, and little is known about the regulation of germinal-centre (GC)-Tfh cell differentiation. Here, authors establish markers in the early precursor stage that distinguish between the GC-Tfh and memory T cell fates and identify an important mechanism that regulates the competitive fitness of the GC-Tfh cells.
- Fangming Zhu
- , Ryan J. McMonigle
- & Hui Hu