Abstract:
:Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
journal_name
Nat Medjournal_title
Nature medicineauthors
Wagar LE,Salahudeen A,Constantz CM,Wendel BS,Lyons MM,Mallajosyula V,Jatt LP,Adamska JZ,Blum LK,Gupta N,Jackson KJL,Yang F,Röltgen K,Roskin KM,Blaine KM,Meister KD,Ahmad IN,Cortese M,Dora EG,Tucker SN,Sperling AIdoi
10.1038/s41591-020-01145-0subject
Has Abstractpub_date
2021-01-01 00:00:00pages
125-135issue
1eissn
1078-8956issn
1546-170Xpii
10.1038/s41591-020-01145-0journal_volume
27pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-mi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1559
更新日期:2007-06-01 00:00:00
abstract::The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and me...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1735
更新日期:2008-05-01 00:00:00
abstract::The present study describes a technique for quantitation of mRNA in a few isotypic cells obtained from an intact organ structure by combining laser-assisted cell picking and real-time PCR. The microscopically controlled lasering of selected cells in stained tissue sections was applied to lung alveolar macrophages, whi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/3327
更新日期:1998-11-01 00:00:00
abstract::Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brai...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2749
更新日期:2012-06-01 00:00:00
abstract::Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/71582
更新日期:2000-01-01 00:00:00
abstract::Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3932
更新日期:2015-10-01 00:00:00
abstract::Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that rates of mitochondria...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3415
更新日期:2014-01-01 00:00:00
abstract::Restriction factors are host cell proteins that inhibit retroviral infection. A new study using mutants of human HIV-1 restriction factor SAMHD1 suggests that it inhibits infection through degradation of viral RNA rather than through its dNTPase activity as previously suggested. ...
journal_title:Nature medicine
pub_type: 评论,杂志文章
doi:10.1038/nm.3657
更新日期:2014-08-01 00:00:00
abstract::Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encod...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3840
更新日期:2015-06-01 00:00:00
abstract::Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3142
更新日期:2013-04-01 00:00:00
abstract::Beta-catenin is a central molecule in the Wnt pathway. Expression of a stable form of beta-catenin on CD4+CD25+ regulatory T (T(reg)) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable beta-catenin-expressing CD4+CD25+ T(reg) cells outcompeted control T(reg) cells in vivo, ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1707
更新日期:2008-02-01 00:00:00
abstract::TRK fusions are found in a variety of cancer types, lead to oncogenic addiction, and strongly predict tumor-agnostic efficacy of TRK inhibition1-8. With the recent approval of the first selective TRK inhibitor, larotrectinib, for patients with any TRK-fusion-positive adult or pediatric solid tumor, to identify mechani...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0542-z
更新日期:2019-09-01 00:00:00
abstract::Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung canc...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0134-3
更新日期:2018-09-01 00:00:00
abstract::Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantiall...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2188
更新日期:2010-08-01 00:00:00
abstract::Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4280
更新日期:2017-03-01 00:00:00
abstract::The World Health Organization estimates that tobacco will become the largest single health problem by 2020, causing an estimated 8.4 million deaths annually. But the smoking burden will not be distributed evenly across the globe; deaths in developed nations are set to rise 50% to 2.4 million while those in Asia will s...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/83281
更新日期:2001-01-01 00:00:00
abstract::Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthrit...
journal_title:Nature medicine
pub_type: 杂志文章,meta分析
doi:10.1038/s41591-020-0833-4
更新日期:2020-06-01 00:00:00
abstract::Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation bet...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm896
更新日期:2003-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-019-0562-8
更新日期:2019-09-01 00:00:00
abstract::Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Her...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm819
更新日期:2003-02-01 00:00:00
abstract::Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plant...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0797-793
更新日期:1997-07-01 00:00:00
abstract::Congenital disorder of glycosylation-Ia (CDG-Ia, also known as PMM2-CDG) is caused by mutations in the gene that encodes phosphomannomutase 2 (PMM2, EC 5.4.2.8) leading to a multisystemic disease with severe psychomotor and mental retardation. In a hypomorphic Pmm2 mouse model, we were able to overcome embryonic letha...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2548
更新日期:2011-12-11 00:00:00
abstract::In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep ta...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0915-3
更新日期:2020-07-01 00:00:00
abstract::Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends almost exclusively on praziquantel. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a quantita...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1737
更新日期:2008-04-01 00:00:00
abstract::Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products. Here we report that the intestinal bacterial microflora and a functional Toll-like receptor 4 (TLR4), but not TLR2, are required for hepatic fibrogenesis. Using Tlr4-chimeric mice and in vivo lipopoly...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1663
更新日期:2007-11-01 00:00:00
abstract::Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0798-848
更新日期:1998-07-01 00:00:00
abstract::Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-deri...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3516
更新日期:2014-05-01 00:00:00
abstract::Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-1123-x
更新日期:2021-01-01 00:00:00
abstract::Neurofibrillary tangles (NFTs), composed of truncated and hyperphosphorylated tau, are a common feature of numerous aging-related neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanisms mediating tau truncation and aggregation during aging remain elusive. Here we show that asp...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3700
更新日期:2014-11-01 00:00:00
abstract::Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2021
更新日期:2009-11-01 00:00:00