Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19.

Abstract:

:The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (TH) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional TH1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.

journal_name

Cell

journal_title

Cell

authors

Meckiff BJ,Ramírez-Suástegui C,Fajardo V,Chee SJ,Kusnadi A,Simon H,Eschweiler S,Grifoni A,Pelosi E,Weiskopf D,Sette A,Ay F,Seumois G,Ottensmeier CH,Vijayanand P

doi

10.1016/j.cell.2020.10.001

subject

Has Abstract

pub_date

2020-11-25 00:00:00

pages

1340-1353.e16

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(20)31307-6

journal_volume

183

pub_type

杂志文章

相关文献

CELL文献大全
  • An Atomic Structure of the Human Spliceosome.

    abstract::Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C∗ complex) at an average resolution of 3.76 Å. The splicing factor Prp17...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2017.04.033

    authors: Zhang X,Yan C,Hang J,Finci LI,Lei J,Shi Y

    更新日期:2017-05-18 00:00:00

  • daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex.

    abstract::daughterless (da) has multiple functions in Drosophila embryonic development: maternal da activity is necessary for proper sex determination, and zygotic da activity is necessary for formation of the peripheral nervous system. We have cloned the region containing da and have found that five recessive lethal da mutatio...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(88)90250-4

    authors: Caudy M,Vässin H,Brand M,Tuma R,Jan LY,Jan YN

    更新日期:1988-12-23 00:00:00

  • Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen.

    abstract::The large tumor antigen (LTag) of simian virus 40, an AAA(+) protein, is a hexameric helicase essential for viral DNA replication in eukaryotic cells. LTag functions as an efficient molecular machine powered by ATP binding and hydrolysis for origin DNA melting and replication fork unwinding. To understand how ATP bind...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2004.09.017

    authors: Gai D,Zhao R,Li D,Finkielstein CV,Chen XS

    更新日期:2004-10-01 00:00:00

  • TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma.

    abstract::Subsets of long-lived, tumor-initiating stem cells often escape cancer therapies. However, sources and mechanisms that generate tumor heterogeneity and drug-resistant cell population are still unfolding. Here, we devise a functional reporter system to lineage trace and/or genetic ablate signaling in TGF-β-activated sq...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2015.01.043

    authors: Oshimori N,Oristian D,Fuchs E

    更新日期:2015-02-26 00:00:00

  • Origins and Proliferative States of Human Oligodendrocyte Precursor Cells.

    abstract::Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown....

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2020.06.027

    authors: Huang W,Bhaduri A,Velmeshev D,Wang S,Wang L,Rottkamp CA,Alvarez-Buylla A,Rowitch DH,Kriegstein AR

    更新日期:2020-08-06 00:00:00

  • Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.

    abstract::A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice. Haplodeficien...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2009.01.020

    authors: Mazzone M,Dettori D,de Oliveira RL,Loges S,Schmidt T,Jonckx B,Tian YM,Lanahan AA,Pollard P,de Almodovar CR,De Smet F,Vinckier S,Aragonés J,Debackere K,Luttun A,Wyns S,Jordan B,Pisacane A,Gallez B,Lampugnani MG,Dej

    更新日期:2009-03-06 00:00:00

  • A hyperconversion mechanism generates the chicken light chain preimmune repertoire.

    abstract::The chicken immunoglobulin light chain repertoire has been shown to be entirely derived from a single V lambda 1-J rearranged combination. The complete coding information of the lambda locus was determined: it comprises 25 V-hybridizing elements, all of which are pseudogenes, clustered in both orientations within 19 k...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(87)90189-9

    authors: Reynaud CA,Anquez V,Grimal H,Weill JC

    更新日期:1987-02-13 00:00:00

  • Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance.

    abstract::Type 2 (non-insulin-dependent) diabetes mellitus is a progressive metabolic disorder arising from genetic and environmental factors that impair beta cell function and insulin action in peripheral tissues. We identified reduced diacylglycerol kinase delta (DGKdelta) expression and DGK activity in skeletal muscle from t...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2007.12.035

    authors: Chibalin AV,Leng Y,Vieira E,Krook A,Björnholm M,Long YC,Kotova O,Zhong Z,Sakane F,Steiler T,Nylén C,Wang J,Laakso M,Topham MK,Gilbert M,Wallberg-Henriksson H,Zierath JR

    更新日期:2008-02-08 00:00:00

  • Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex.

    abstract::Telomeres of Oxytricha nova macronuclear chromosomes consist of a repeated T4G4 sequence, single-stranded at the 3' terminus, bound by a heterodimeric protein. The cloning of genes for the two polypeptides and their separate expression in E. coli have enabled evaluation of their individual contributions to DNA binding...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(91)90075-a

    authors: Gray JT,Celander DW,Price CM,Cech TR

    更新日期:1991-11-15 00:00:00

  • Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly.

    abstract::Kinetochores connect centromeric nucleosomes with mitotic-spindle microtubules through conserved, cross-interacting protein subassemblies. In budding yeast, the heterotetrameric MIND complex (Mtw1, Nnf1, Nsl1, Dsn1), ortholog of the metazoan Mis12 complex, joins the centromere-proximal components, Mif2 and COMA, with ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2016.10.011

    authors: Dimitrova YN,Jenni S,Valverde R,Khin Y,Harrison SC

    更新日期:2016-11-03 00:00:00

  • Isolation and characterization of the nuclear matrix in Friend erythroleukemia cells: chromatin and hnRNA interactions with the nuclear matrix.

    abstract::Nuclear matrices from undifferentiated and differentiated Friend erythroleukemia cells have been obtained by a method which removes DNA in a physiological buffer. These matrices preserved the characteristic topographical distribution of condensed and diffuse "chromatin" regions, as do nuclei in situ or isolated nuclei...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(79)90221-6

    authors: Long BH,Huang CY,Pogo AO

    更新日期:1979-12-01 00:00:00

  • Mini-P1 plasmid replication: the autoregulation-sequestration paradox.

    abstract::It has been proposed that the initiator protein RepA is rate limiting for mini-P1 plasmid replication, and that the role of the plasmid copy number control locus is to sequester the initiator and thus reduce replication. This proposal appears inconsistent with the observation that RepA is autoregulated, since the prot...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(88)90468-0

    authors: Chattoraj DK,Mason RJ,Wickner SH

    更新日期:1988-02-26 00:00:00

  • Multilevel modulation of a sensory motor circuit during C. elegans sleep and arousal.

    abstract::Sleep is characterized by behavioral quiescence, homeostasis, increased arousal threshold, and rapid reversibility. Understanding how these properties are encoded by a neuronal circuit has been difficult, and no single molecular or neuronal pathway has been shown to be responsible for the regulation of sleep. Taking a...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.11.036

    authors: Cho JY,Sternberg PW

    更新日期:2014-01-16 00:00:00

  • Retinoic acid signaling is essential for embryonic hematopoietic stem cell development.

    abstract::Hematopoietic stem cells (HSCs) develop from a specialized subpopulation of endothelial cells known as hemogenic endothelium (HE). Although the HE origin of HSCs is now well established in different species, the signaling pathways that control this transition remain poorly understood. Here, we show that activation of ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.08.055

    authors: Chanda B,Ditadi A,Iscove NN,Keller G

    更新日期:2013-09-26 00:00:00

  • The evolution of adaptive immune systems.

    abstract::A clonally diverse anticipatory repertoire in which each lymphocyte bears a unique antigen receptor is the central feature of the adaptive immune system that evolved in our vertebrate ancestors. The survival advantage gained through adding this type of adaptive immune system to a pre-existing innate immune system led ...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2006.02.001

    authors: Cooper MD,Alder MN

    更新日期:2006-02-24 00:00:00

  • Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.

    abstract::The immunological synapse (IS) is a junction between the T cell and antigen-presenting cell and is composed of supramolecular activation clusters (SMACs). No studies have been published on naive T cell IS dynamics. Here, we find that IS formation during antigen recognition comprises cycles of stable IS formation and a...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2007.03.037

    authors: Sims TN,Soos TJ,Xenias HS,Dubin-Thaler B,Hofman JM,Waite JC,Cameron TO,Thomas VK,Varma R,Wiggins CH,Sheetz MP,Littman DR,Dustin ML

    更新日期:2007-05-18 00:00:00

  • Nucleotide sequence of the triosephosphate isomerase gene from Aspergillus nidulans: implications for a differential loss of introns.

    abstract::A functional cDNA from Aspergillus nidulans encoding triosephosphate isomerase (TPI) was isolated by its ability to complement a tpi1 mutation in Saccharomyces cerevisiae. This cDNA was used to obtain the corresponding gene, tpiA. Alignment of the cDNA and genomic DNA nucleotide sequences indicated that tpiA contains ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90868-8

    authors: McKnight GL,O'Hara PJ,Parker ML

    更新日期:1986-07-04 00:00:00

  • Conformational changes in a replication origin induced by an initiator protein.

    abstract::The replication initiator protein of the plasmid R6K binds to seven contiguous 22 bp direct repeats that form an indispensable part of the three replication origins alpha, beta, and gamma. Binding of the initiator to the direct repeats induced a marked bending of the region of gamma replication origin. Binding of the ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(85)90023-6

    authors: Mukherjee S,Patel I,Bastia D

    更新日期:1985-11-01 00:00:00

  • The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.

    abstract::Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2017.01.024

    authors: Fédry J,Liu Y,Péhau-Arnaudet G,Pei J,Li W,Tortorici MA,Traincard F,Meola A,Bricogne G,Grishin NV,Snell WJ,Rey FA,Krey T

    更新日期:2017-02-23 00:00:00

  • The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter.

    abstract::Fractionation of HeLa cell extracts reveals the presence of a promoter-specific transcription factor, Sp 1, which activates a class of promoters that includes the SV40 early promoter but not several others that have been tested. We analyzed SV40 early-promoter deletion mutants and determined that transcriptional activ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(83)90210-6

    authors: Dynan WS,Tjian R

    更新日期:1983-11-01 00:00:00

  • Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4.

    abstract::In nearly every organism studied, reduced caloric intake extends life span. In yeast, span extension from dietary restriction is thought to be mediated by the highly conserved, nutrient-responsive target of rapamycin (TOR), protein kinase A (PKA), and Sch9 kinases. These kinases coordinately regulate various cellular ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2008.02.037

    authors: Steffen KK,MacKay VL,Kerr EO,Tsuchiya M,Hu D,Fox LA,Dang N,Johnston ED,Oakes JA,Tchao BN,Pak DN,Fields S,Kennedy BK,Kaeberlein M

    更新日期:2008-04-18 00:00:00

  • Architecture and membrane interactions of the EGF receptor.

    abstract::Dimerization-driven activation of the intracellular kinase domains of the epidermal growth factor receptor (EGFR) upon extracellular ligand binding is crucial to cellular pathways regulating proliferation, migration, and differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting that the mechanis...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2012.12.030

    authors: Arkhipov A,Shan Y,Das R,Endres NF,Eastwood MP,Wemmer DE,Kuriyan J,Shaw DE

    更新日期:2013-01-31 00:00:00

  • Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.

    abstract::Vascular permeability is frequently associated with inflammation and is triggered by a cohort of secreted permeability factors such as vascular endothelial growth factor (VEGF). Here, we show that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) an...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.12.025

    authors: Goddard LM,Murphy TJ,Org T,Enciso JM,Hashimoto-Partyka MK,Warren CM,Domigan CK,McDonald AI,He H,Sanchez LA,Allen NC,Orsenigo F,Chao LC,Dejana E,Tontonoz P,Mikkola HK,Iruela-Arispe ML

    更新日期:2014-01-30 00:00:00

  • The initiation sites for RNA transcription in Ad2 DNA.

    abstract::Six restriction fragments of Ad2 DNA which contain sites for RNA initiation have been identified by their ability to hybridize nascent labeled RNA less than 1 kb in length. Four RNA initiation sites early in infection are identified in regions where previous work (Flint, 1977) had mapped mRNAs. The major late RNA init...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(77)90273-2

    authors: Evans RM,Fraser N,Ziff E,Weber J,Wilson M,Darnell JE

    更新日期:1977-11-01 00:00:00

  • Linking retroelements to autoimmunity.

    abstract::In this issue, Stetson et al. (2008) report a mechanism by which host cells avert an autoimmune response to self-nucleic acids. They show that the nuclease Trex1 prevents the accumulation of DNA derived from endogenous retroelements that, if left unchecked, trigger elevated production of type I interferons leading to ...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2008.08.010

    authors: Bhoj VG,Chen ZJ

    更新日期:2008-08-22 00:00:00

  • On the nature of tetracycline resistance controlled by the plasmid pSC101.

    abstract::In vitro enzymatic alteration of plasmid phenotype and in vitro construction of recombinant plasmids containing genetic information derived from the plasmid pSC101 have been used to investigate the mechanism of function of tetracycline resistance determined by the plasmid pSC101. The resistance has been shown to be in...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(78)90139-3

    authors: Tait RC,Boyer HW

    更新日期:1978-01-01 00:00:00

  • How TriC folds tricky proteins.

    abstract::How chaperonins orchestrate the successful folding of even the most elaborate of proteins is a question of central importance. In two recent studies in Cell by Joachimiak et al. and Freund et al., a new class of TRiC substrate is identified, and how the chaperonin exploits its different subunits to extend its substrat...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2014.11.029

    authors: Zhuravleva A,Radford SE

    更新日期:2014-12-04 00:00:00

  • The interaction of estradiol-receptor protein with the genome: an argument for the existence of undetected specific sites.

    abstract::In extracts from rat and calf uterus, the steroid hormone 17 beta-estradiol stimulates the binding of its specific receptor protein to DNA. This interaction appears to be of low affinity (half of the estradiol-activated, 5S receptor bound at 300-400 mug/ml DNA) and nonspecific with respect to DNA base sequence. No bin...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(75)90150-6

    authors: Yamamoto K,Alberts B

    更新日期:1975-04-01 00:00:00

  • Splice modulating therapies for human disease.

    abstract::Dysregulation of splicing and alternative splicing underlies many genetic and acquired diseases. We present an overview of recent strategies and successes in modulating splicing therapeutically in clinical and preclinical contexts. Effective approaches include restoring open reading frames, influencing alternative spl...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2012.02.014

    authors: Spitali P,Aartsma-Rus A

    更新日期:2012-03-16 00:00:00

  • Gut microbiota: the link to your second brain.

    abstract::Serotonin is a highly ubiquitous signaling molecule that plays a role in the regulation of various physiological functions. Several lines of evidence, including the present work from Hsiao and colleagues, demonstrate that, in the gut, microbial-derived metabolites affect the production of serotonin that in turn impact...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2015.03.033

    authors: Ridaura V,Belkaid Y

    更新日期:2015-04-09 00:00:00