Naïve CD8+ T-Cells Engage a Versatile Metabolic Program Upon Activation in Humans and Differ Energetically From Memory CD8+ T-Cells.

Abstract:

:Background: Characterization of the intracellular biochemical processes that regulate the generation and maintenance of effector and memory CD8+ T-cells from naïve precursors is essential for our understanding of adaptive immune responses and the development of immunotherapies. However, the metabolic determinants of antigen-driven activation and differentiation remain poorly defined, especially in humans. Methods: We used a variety of different approaches, including gene expression profiling and measurements of nutrient flux, to characterize the basal and activation-induced energetic requirements of naïve and phenotypically-defined subsets of human memory CD8+ T-cells. Findings: Profound metabolic differences were apparent as a function of differentiation status, both at rest and in response to stimulation via the T cell receptor (TCR). Of particular note, resting naïve CD8+ T cells were largely quiescent, but rapidly upregulated diverse energetic pathways after ligation of surface-expressed TCRs. Moreover, autophagy and the mechanistic target of rapamycin (mTOR)-dependent glycolytic pathway were identified as critical mediators of antigen-driven priming in the naïve CD8+ T cell pool, the efficiency of which was dampened by the presence of neutral lipids and fatty acids. Interpretation: These observations provide a metabolic roadmap of the CD8+ T-cell compartment in humans and reveal potentially selective targets for novel immunotherapies.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Nicoli F,Papagno L,Frere JJ,Cabral-Piccin MP,Clave E,Gostick E,Toubert A,Price DA,Caputo A,Appay V

doi

10.3389/fimmu.2018.02736

subject

Has Abstract

pub_date

2018-12-21 00:00:00

pages

2736

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • Alum/Toll-Like Receptor 7 Adjuvant Enhances the Expansion of Memory B Cell Compartment Within the Draining Lymph Node.

    abstract::Vaccination is one of the most cost-effective health interventions and, with the exception of water sanitization, no other action has had such a major effect in mortality reduction. Combined with other approaches, such as clean water, better hygiene, and health education, vaccination contributed to prevent millions of...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00641

    authors: Vo HTM,Baudner BC,Sammicheli S,Iannacone M,D'Oro U,Piccioli D

    更新日期:2018-04-09 00:00:00

  • Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats.

    abstract::Depression is considered a neuropsychiatric disease associated with various neuronal changes within specific brain regions. We previously reported that ginsenoside-Rg1, a potential neuroprotective agent extracted from ginseng, significantly alleviated depressive-like disorders induced by chronic stress in rats. Howeve...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02889

    authors: Fan C,Song Q,Wang P,Li Y,Yang M,Yu SY

    更新日期:2018-12-07 00:00:00

  • Antifungal Immunological Defenses in Newborns.

    abstract::Newborns are prone to fungal infections, largely due to Candida species. The immunological basis for this vulnerability is not yet fully understood. However, useful insights can be gained from the knowledge of the maturation of immune pathways during ontogeny, particularly when placed in context with how rare genetic ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00281

    authors: Michalski C,Kan B,Lavoie PM

    更新日期:2017-03-15 00:00:00

  • Exploitation of Neisseria meningitidis Group B OMV Vaccines Against N. gonorrhoeae to Inform the Development and Deployment of Effective Gonorrhea Vaccines.

    abstract::Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00683

    authors: Petousis-Harris H,Radcliff FJ

    更新日期:2019-04-09 00:00:00

  • Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes.

    abstract::Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists betwee...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.551758

    authors: Zaric BL,Radovanovic JN,Gluvic Z,Stewart AJ,Essack M,Motwalli O,Gojobori T,Isenovic ER

    更新日期:2020-09-28 00:00:00

  • AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases.

    abstract::A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-ass...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01487

    authors: Wang L,Sun L,Byrd KM,Ko CC,Zhao Z,Fang J

    更新日期:2020-08-13 00:00:00

  • Several Follicular Regulatory T Cell Subsets With Distinct Phenotype and Function Emerge During Germinal Center Reactions.

    abstract::An efficient B cell immunity requires a dynamic equilibrium between positive and negative signals. In germinal centers (GCs), T follicular helper cells are supposed to be the positive regulator while T follicular regulatory (Tfr) cells were assigned to be the negative regulators. Indeed, Tfr cells are considered as a ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01792

    authors: Fazilleau N,Aloulou M

    更新日期:2018-08-13 00:00:00

  • Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunotherapy.

    abstract::Recent clinical observations indicate that bacterial vaccines induce cross-protection against infections produced by different microorganisms. MV130, a polyvalent bacterial sublingual preparation designed to prevent recurrent respiratory infectious diseases, reduces the infection rate in patients with recurrent respir...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.567391

    authors: Vázquez A,Fernández-Sevilla LM,Jiménez E,Pérez-Cabrera D,Yañez R,Subiza JL,Varas A,Valencia J,Vicente A

    更新日期:2020-11-19 00:00:00

  • CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV.

    abstract::Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02310

    authors: Kim GB,Hege K,Riley JL

    更新日期:2019-09-27 00:00:00

  • Novel Chimeric Protein Vaccines Against Clostridium difficile Infection.

    abstract::Clostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comprised of the glucos...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02440

    authors: Wang S,Wang Y,Cai Y,Kelly CP,Sun X

    更新日期:2018-10-22 00:00:00

  • MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice.

    abstract::Infections with respiratory syncytial virus (RSV) occurs repeatedly throughout life because sustained, protective memory responses fail to develop. Why this occurs is not known. During RSV infection the recognition of the virus via the cytosolic RIG-I like receptors and signaling via the adaptor protein MAVS is crucia...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.572747

    authors: Paulsen M,Varese A,Pinpathomrat N,Kirsebom FCM,Paulsen M,Johansson C

    更新日期:2020-10-06 00:00:00

  • Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite.

    abstract::Plasmodium vivax is the most common species that cause malaria outside of the African continent. The development of an efficacious vaccine would contribute greatly to control malaria. Recently, using bacterial and adenoviral recombinant proteins based on the P. vivax circumsporozoite protein (CSP), we demonstrated the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01275

    authors: Gimenez AM,Lima LC,Françoso KS,Denapoli PMA,Panatieri R,Bargieri DY,Thiberge JM,Andolina C,Nosten F,Renia L,Nussenzweig RS,Nussenzweig V,Amino R,Rodrigues MM,Soares IS

    更新日期:2017-10-11 00:00:00

  • Modulation of Chemokine Responses: Synergy and Cooperativity.

    abstract::Chemokine biology is mediated by more complex interactions than simple monomolecular ligand-receptor interactions, as chemokines can form higher order quaternary structures, which can also be formed after binding to glycosaminoglycans (GAGs) on endothelial cells, and their receptors are found as dimers and/or oligomer...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00183

    authors: Proudfoot AE,Uguccioni M

    更新日期:2016-05-19 00:00:00

  • Estrogen Receptor Alpha Signaling Is Responsible for the Female Sex Bias in the Loss of Tolerance and Immune Cell Activation Induced by the Lupus Susceptibility Locus Sle1b.

    abstract::The dramatic female sex bias observed in human lupus is thought to be due, at least in part, to estrogens. Using mouse models, we have shown that estrogens, acting through estrogen receptor alpha (ERα) promote lupus development and contribute significantly to the female sex bias observed in this disease. C57Bl/6 (B6) ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.582214

    authors: Graham JH,Yoachim SD,Gould KA

    更新日期:2020-11-10 00:00:00

  • Time and Demand are Two Critical Dimensions of Immunometabolism: The Process of Macrophage Activation and the Pentose Phosphate Pathway.

    abstract::A process is a function of time; in immunometabolism, this is reflected by the stepwise adaptation of metabolism to sustain the bio-energetic demand of an immune-response in its various states and shades. This perspective article starts by presenting an early attempt to investigate the physiology of inflammation, in o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00164

    authors: Nagy C,Haschemi A

    更新日期:2015-04-08 00:00:00

  • ATP-Induced Inflammasome Activation and Pyroptosis Is Regulated by AMP-Activated Protein Kinase in Macrophages.

    abstract::Adenosine triphosphate (ATP) is released by bacteria and host cells during bacterial infection as well as sterile tissue injury, acting as an inducer of inflammasome activation. Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. However, it is unclear whether AMPK s...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00597

    authors: Zha QB,Wei HX,Li CG,Liang YD,Xu LH,Bai WJ,Pan H,He XH,Ouyang DY

    更新日期:2016-12-12 00:00:00

  • Thioredoxin Modulates Protein Arginine Deiminase 4 (PAD4)-Catalyzed Citrullination.

    abstract::Protein citrullination is a post-translational modification catalyzed by the protein arginine deiminases (PADs). This modification plays a crucial role in the pathophysiology of numerous autoimmune disorders including RA. Recently, there has been a growing interest in investigating physiological regulators of PAD acti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00244

    authors: Nagar M,Tilvawala R,Thompson PR

    更新日期:2019-02-19 00:00:00

  • Role of C5b-9 and RGC-32 in Cancer.

    abstract::The complement system represents an effective arsenal of innate immunity as well as an interface between innate and adaptive immunity. Activation of the complement system culminates with the assembly of the C5b-9 terminal complement complex on cell membranes, inducing target cell lysis. Translation of this sequence of...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01054

    authors: Vlaicu SI,Tatomir A,Rus V,Rus H

    更新日期:2019-05-09 00:00:00

  • Non-canonical Functions of Macroautophagy Proteins During Endocytosis by Myeloid Antigen Presenting Cells.

    abstract::Endocytosis by myeloid antigen presenting cells such as dendritic cells and macrophages regulates both antigen processing and major histocompatibility complex (MHC) molecule trafficking during antigen presentation. The molecular machinery of macroautophagy, a catabolic pathway that delivers cytoplasmic constituents to...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02765

    authors: Münz C

    更新日期:2018-11-27 00:00:00

  • Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection.

    abstract::Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies w...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01673

    authors: Eichinger KM,Kosanovich JL,Gidwani SV,Zomback A,Lipp MA,Perkins TN,Oury TD,Petrovsky N,Marshall CP,Yondola MA,Empey KM

    更新日期:2020-07-29 00:00:00

  • Interferon Signaling Is Frequently Downregulated in Melanoma.

    abstract::Immune checkpoint inhibitors that block the programmed cell death protein 1/PD-L1 pathway have significantly improved the survival of patients with advanced melanoma. Immunotherapies are only effective in 15-40% of melanoma patients and resistance is associated with defects in antigen presentation and interferon signa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01414

    authors: Alavi S,Stewart AJ,Kefford RF,Lim SY,Shklovskaya E,Rizos H

    更新日期:2018-06-21 00:00:00

  • Tfh1 Cells in Germinal Centers During Chronic HIV/SIV Infection.

    abstract::T follicular helper CD4 cells (Tfh) are essential for the development and maintenance of germinal center (GC) reactions, a critical process that promotes the generation of long-lived high affinity humoral immunity. It is becoming increasingly evident that GC-Tfh cells are heterogeneous in nature with some cellular cha...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01272

    authors: Velu V,Mylvaganam G,Ibegbu C,Amara RR

    更新日期:2018-06-06 00:00:00

  • Gene Expression Profiling of PDGFRA Mutant GIST Reveals Immune Signatures as a Specific Fingerprint of D842V Exon 18 Mutation.

    abstract::Platelet Derived Growth Factor Receptor Alpha (PDGFRA) mutations occur in only about 5-7% of gastrointestinal stromal tumors (GIST), notably with alterations on exons 12/14/18. The most frequent PDGFRA mutation is the exon 18 D842V, which is correlated to specific clinico-pathological features, such as primary imatini...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00851

    authors: Indio V,Ravegnini G,Astolfi A,Urbini M,Saponara M,De Leo A,Gruppioni E,Tarantino G,Angelini S,Pession A,Pantaleo MA,Nannini M

    更新日期:2020-06-02 00:00:00

  • Impaired Control of Epstein-Barr Virus Infection in B-Cell Expansion with NF-κB and T-Cell Anergy Disease.

    abstract::B-cell expansion with NF-κB and T-cell anergy (BENTA) disease is a B-cell-specific lymphoproliferative disorder caused by germline gain-of-function mutations in CARD11. These mutations force the CARD11 scaffold into an open conformation capable of stimulating constitutive NF-κB activation in lymphocytes, without requi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00198

    authors: Arjunaraja S,Angelus P,Su HC,Snow AL

    更新日期:2018-02-08 00:00:00

  • Neuroimmunology of Behavioral Comorbidities Associated With Cancer and Cancer Treatments.

    abstract::Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after variou...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01195

    authors: Santos JC,Pyter LM

    更新日期:2018-06-07 00:00:00

  • Human Tregs Made Antigen Specific by Gene Modification: The Power to Treat Autoimmunity and Antidrug Antibodies with Precision.

    abstract::Human regulatory CD4+ T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. T...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01117

    authors: Adair PR,Kim YC,Zhang AH,Yoon J,Scott DW

    更新日期:2017-09-21 00:00:00

  • Tumor-Associated Neutrophils and Macrophages-Heterogenous but Not Chaotic.

    abstract::Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) have been extensively studied. Their pleotropic roles were observed in multiple steps of tumor progression and metastasis, and sometimes appeared to be inconsistent across different studies. In this review, we collectively discussed many lines...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.553967

    authors: Wu L,Zhang XH

    更新日期:2020-12-02 00:00:00

  • l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes.

    abstract::A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We ha...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00487

    authors: Yu HR,Tsai CC,Chang LS,Huang HC,Cheng HH,Wang JY,Sheen JM,Kuo HC,Hsieh KS,Huang YH,Yang KD,Hsu TY

    更新日期:2017-04-25 00:00:00

  • Structure Based Refinement of a Humanized Monoclonal Antibody That Targets Tumor Antigen Disialoganglioside GD2.

    abstract::Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antib...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2014.00372

    authors: Ahmed M,Hu J,Cheung NK

    更新日期:2014-08-14 00:00:00

  • Interleukin-1/-33 Signaling Pathways as Therapeutic Targets for Endometriosis.

    abstract::Endometriosis is an estrogen-dependent disease with symptoms of dysmenorrhea, chronic pain, and infertility that affects 6-10% of women of reproductive age. Medical or surgical therapy, such as administration of an anti-gonadotropin or ovarian cystectomy, provide effective pain relief. However, neither therapy can be ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02021

    authors: Kato T,Yasuda K,Matsushita K,Ishii KJ,Hirota S,Yoshimoto T,Shibahara H

    更新日期:2019-08-22 00:00:00