CD8+HLADR+ Regulatory T Cells Change With Aging: They Increase in Number, but Lose Checkpoint Inhibitory Molecules and Suppressive Function.

Abstract:

:CD4+ regulatory T cells have been intensively studied during aging, but little is still known about age-related changes of other regulatory T cell subsets. It was, therefore, the goal of the present study to analyze CD8+human leukocyte antigen-antigen D related (HLADR)+ T cells in old age, a cell population reported to have suppressive activity and to be connected to specific genetic variants. We demonstrate a strong increase in the number of CD8+HLADR+ T cells with age in a cohort of female Sardinians as well as in elderly male and female persons from Austria. We also show that CD8+HLADR+ T cells lack classical activation molecules, such as CD69 and CD25, but contain increased numbers of checkpoint inhibitory molecules, such as cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin and mucin protein-3, LAG-3, and PD-1, when compared with their HLADR- counterparts. They also have the capacity to inhibit the proliferation of autologous peripheral blood mononuclear cells. This suppressive activity is, however, decreased when CD8+HLADR+ T cells from elderly persons are analyzed. In accordance with this finding, CD8+HLADR+ T cells from persons of old age contain lower percentages of checkpoint inhibitory molecules than young controls. We conclude that in spite of high abundance of a CD8+ regulatory T cell subset in old age its expression of checkpoint inhibitory molecules and its suppressive function on a per cell basis are reduced. Reduction of suppressive capacity may support uncontrolled subclinical inflammatory processes referred to as "inflamm-aging."

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Lukas Yani S,Keller M,Melzer FL,Weinberger B,Pangrazzi L,Sopper S,Trieb K,Lobina M,Orrù V,Fiorillo E,Cucca F,Grubeck-Loebenstein B

doi

10.3389/fimmu.2018.01201

subject

Has Abstract

pub_date

2018-06-04 00:00:00

pages

1201

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • O-Serotype Conversion in Salmonella Typhimurium Induces Protective Immune Responses against Invasive Non-Typhoidal Salmonella Infections.

    abstract::Salmonella infections remain a big problem worldwide, causing enteric fever by Salmonella Typhi (or Paratyphi) or self-limiting gastroenteritis by non-typhoidal Salmonella (NTS) in healthy individuals. NTS may become invasive and cause septicemia in elderly or immuno-compromised individuals, leading to high mortality ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01647

    authors: Li P,Liu Q,Luo H,Liang K,Yi J,Luo Y,Hu Y,Han Y,Kong Q

    更新日期:2017-12-04 00:00:00

  • Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis.

    abstract::Background: Alemtuzumab is a highly effective drug for the treatment of multiple sclerosis (MS), characterized by specific patterns of depletion and repopulation. As an induction-like treatment concept, two mandatory infusion courses can inhibit long-term disease activity in the majority of patients, and additional co...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00056

    authors: Akgün K,Blankenburg J,Marggraf M,Haase R,Ziemssen T

    更新日期:2020-01-31 00:00:00

  • IL-10/STAT3/SOCS3 Axis Is Involved in the Anti-inflammatory Effect of Benznidazole.

    abstract::Anti-parasitic treatment for Chagas disease mainly relies on benznidazole, which is virtually the only drug available in the market. Besides its anti-parasitic effects, benznidazole has anti-inflammatory properties. In this work we studied the mechanisms involved in the latter, demonstrating the participation of the I...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01267

    authors: Cevey ÁC,Penas FN,Alba Soto CD,Mirkin GA,Goren NB

    更新日期:2019-06-04 00:00:00

  • Pentraxin 3: an immuno-regulator in the lungs.

    abstract::Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that is a humoral component of the innate immune system. It interacts with pathogenic moieties, infected and dying host cells and facilitates their removal through activation of appropriate innate and adaptive mechanisms. PTX3 is secreted by a diverse variet...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00127

    authors: Balhara J,Koussih L,Zhang J,Gounni AS

    更新日期:2013-05-31 00:00:00

  • IL-23 Contributes to Campylobacter jejuni-Induced Intestinal Pathology via Promoting IL-17 and IFNγ Responses by Innate Lymphoid Cells.

    abstract::Human pathogen Campylobacter jejuni is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in C. jejuni-d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.579615

    authors: Jing X,Korchagina AA,Shein SA,Muraoka WT,Koroleva E,Tumanov AV

    更新日期:2021-01-06 00:00:00

  • Antimicrobial Proteins and Peptides in Early Life: Ontogeny and Translational Opportunities.

    abstract::While developing adaptive immune responses, young infants are especially vulnerable to serious infections, including sepsis, meningitis, and pneumonia. Antimicrobial proteins and peptides (APPs) are key effectors that function as broad-spectrum anti-infectives. This review seeks to summarize the clinically relevant fu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00309

    authors: Battersby AJ,Khara J,Wright VJ,Levy O,Kampmann B

    更新日期:2016-08-18 00:00:00

  • Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy.

    abstract::Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02467

    authors: Toscani D,Bolzoni M,Ferretti M,Palumbo C,Giuliani N

    更新日期:2018-10-24 00:00:00

  • Crispr/Cas Mediated Deletion of PTPN22 in Jurkat T Cells Enhances TCR Signaling and Production of IL-2.

    abstract::A single nucleotide polymorphism, C1858T, in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) results in one of the strongest genetic traits associated with autoimmune disease outside of the Major Histocompatibility Complex (MHC) genes. However, the consequences of this polymorphism, whi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02595

    authors: Bray C,Wright D,Haupt S,Thomas S,Stauss H,Zamoyska R

    更新日期:2018-11-12 00:00:00

  • Myeloid-Derived Suppressor Cell-Derived Arginase-1 Oppositely Modulates IL-17A and IL-17F Through the ESR/STAT3 Pathway During Colitis in Mice.

    abstract::Myeloid-derived suppressor cells (MDSC) play a crucial role in regulating the intestinal immune response during colitis. We previously revealed an essential role of MDSC in promoting TH17 cell polarization, which was found to be arginase-1 (Arg-1)-dependent; however, the underlying mechanism remains obscure. Here we r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00687

    authors: Ma Z,Zhen Y,Hu C,Yi H

    更新日期:2020-04-22 00:00:00

  • Gut Microbiota Species Can Provoke both Inflammatory and Tolerogenic Immune Responses in Human Dendritic Cells Mediated by Retinoic Acid Receptor Alpha Ligation.

    abstract::Dendritic cells are considered as the main coordinators of both mucosal and systemic immune responses, thus playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how primary human monocyte-derived DC (moDC) populations drive the polarization of helper T (Th) cells...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00427

    authors: Bene K,Varga Z,Petrov VO,Boyko N,Rajnavolgyi E

    更新日期:2017-04-18 00:00:00

  • T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response.

    abstract::Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is n...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00332

    authors: Aragoneses-Fenoll L,Ojeda G,Montes-Casado M,Acosta-Ampudia Y,Dianzani U,Portolés P,Rojo JM

    更新日期:2018-02-27 00:00:00

  • Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology.

    abstract::Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00140

    authors: Loewendorf AI,Matynia A,Saribekyan H,Gross N,Csete M,Harrington M

    更新日期:2016-04-19 00:00:00

  • Antiphospholipid Syndrome Nephropathy: From Pathogenesis to Treatment.

    abstract::Kidney damage is a well-recognized complication of the antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-associated APS. Kidney involvement in APS involves a variety of manifestations, such as renal artery thrombosis or stenosis, renal vein thrombosis, allograft loss due to thrombos...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01181

    authors: Tektonidou MG

    更新日期:2018-05-31 00:00:00

  • Protein Deiminase 4 and CR3 Regulate Aspergillus fumigatus and β-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3.

    abstract::Neutrophil extracellular trap (NET) formation requires chromatin decondensation before nuclear swelling and eventual extracellular release of DNA, which occurs together with nuclear and cytoplasmic antimicrobial proteins. A key mediator of chromatin decondensation is protein deiminase 4 (PAD4), which catalyzes histone...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01182

    authors: Clark HL,Abbondante S,Minns MS,Greenberg EN,Sun Y,Pearlman E

    更新日期:2018-05-29 00:00:00

  • Cell of Origin and Genetic Alterations in the Pathogenesis of Multiple Myeloma.

    abstract::B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the end product is most commonly humoral immunity, the rapid proliferation and somatic mutation of the B cell receptor also results in oncogenic mutations...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01121

    authors: Barwick BG,Gupta VA,Vertino PM,Boise LH

    更新日期:2019-05-21 00:00:00

  • IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction.

    abstract::Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,随机对照试验

    doi:10.3389/fimmu.2018.02035

    authors: Orrem HL,Nilsson PH,Pischke SE,Kleveland O,Yndestad A,Ekholt K,Damås JK,Espevik T,Bendz B,Halvorsen B,Gregersen I,Wiseth R,Andersen GØ,Ueland T,Gullestad L,Aukrust P,Barratt-Due A,Mollnes TE

    更新日期:2018-09-12 00:00:00

  • A DNA Vaccine in Which the RSV-F Ectodomain Is Covalently Linked to the Burkholderia pseudomallei Antigens TssM and Hcp1 Augments the Humoral and Cytotoxic Response in Mice.

    abstract::DNA vaccines have great potential to control infectious disease, particularly those caused by intracellular organisms. They are inexpensive to produce and can be quickly modified to combat emerging infectious threats, but often fail to generate a strong immunologic response limiting enthusiasm for their use in humans ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02411

    authors: Solodushko V,Bitko V,Barrington R,Fouty B

    更新日期:2019-10-11 00:00:00

  • ERdj5 in Innate Immune Cells Is a Crucial Factor for the Mucosal Adjuvanticity of Cholera Toxin.

    abstract::Cholera toxin (CT) is one of most strong mucosal adjuvants, but it cannot be clinically used owing to its toxicity. The cytosolic A1 subunit of CT (CTA1) is the molecule responsible for its immunostimulatory activity, which increases the concentration of cyclic AMP and causes the induction of pro-inflammatory cytokine...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01249

    authors: Kim MS,Yi EJ,Kim YI,Kim SH,Jung YS,Kim SR,Iwawaki T,Ko HJ,Chang SY

    更新日期:2019-06-04 00:00:00

  • Effects of the Positive Threshold and Data Analysis on Human MOG Antibody Detection by Live Flow Cytometry.

    abstract::Human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have become a useful clinical biomarker for the diagnosis of a spectrum of inflammatory demyelinating disorders. Live cell-based assays that detect MOG Ab against conformational MOG are currently the gold standard. Flow cytometry, in which ser...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00119

    authors: Tea F,Pilli D,Ramanathan S,Lopez JA,Merheb V,Lee FXZ,Zou A,Liyanage G,Bassett CB,Thomsen S,Reddel SW,Barnett MH,Brown DA,Dale RC,Brilot F,Australasian New Zealand MOG Study Group.

    更新日期:2020-02-06 00:00:00

  • IgA and FcαRI: Pathological Roles and Therapeutic Opportunities.

    abstract::Immunoglobulin A (IgA) is the most abundant antibody class present at mucosal surfaces. The production of IgA exceeds the production of all other antibodies combined, supporting its prominent role in host-pathogen defense. IgA closely interacts with the intestinal microbiota to enhance its diversity, and IgA has a pas...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00553

    authors: Breedveld A,van Egmond M

    更新日期:2019-03-22 00:00:00

  • Intravital Multiphoton Microscopy of the Ocular Surface: Alterations in Conventional Dendritic Cell Morphology and Kinetics in Dry Eye Disease.

    abstract::Dry eye disease (DED) is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis and ocular symptoms, in which neurosensory abnormalities have recently been shown to play an etiological role. Although the role of inflammation has been widely studied in DED, the kinetics of immune...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00742

    authors: Jamali A,Seyed-Razavi Y,Chao C,Ortiz G,Kenyon B,Blanco T,Harris DL,Hamrah P

    更新日期:2020-05-07 00:00:00

  • Structure-Function Implications of the Ability of Monoclonal Antibodies Against α-Galactosylceramide-CD1d Complex to Recognize β-Mannosylceramide Presentation by CD1d.

    abstract::iNKT cells are CD1d-restricted T cells recognizing lipid antigens. The prototypic iNKT cell-agonist α-galactosylceramide (α-GalCer) alongside compounds with similar structures induces robust proliferation and cytokine production of iNKT cells and protects against cancer in vivo. Monoclonal antibodies (mAbs) that detec...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02355

    authors: Clark K,Yau J,Bloom A,Wang J,Venzon DJ,Suzuki M,Pasquet L,Compton BJ,Cardell SL,Porcelli SA,Painter GF,Zajonc DM,Berzofsky JA,Terabe M

    更新日期:2019-10-09 00:00:00

  • NKT-Like (CD3+CD56+) Cells in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors.

    abstract::Therapy with Tyrosine Kinase Inhibitors (TKI) aiming stable deep molecular response is the gold standard to treat Chronic Myeloid Leukemia (CML). NKT-like cells (CD3+CD56+) combine characteristics of T and NK cells. The physiopathological role of these cells remains unknown although the literature refers their associa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02493

    authors: Almeida JS,Couceiro P,López-Sejas N,Alves V,Růžičková L,Tarazona R,Solana R,Freitas-Tavares P,Santos-Rosa M,Rodrigues-Santos P

    更新日期:2019-10-22 00:00:00

  • Immune Tolerance Maintained by Cooperative Interactions between T Cells and Antigen Presenting Cells Shapes a Diverse TCR Repertoire.

    abstract::The T cell population in an individual needs to avoid harmful activation by self peptides while maintaining the ability to respond to an unknown set of foreign peptides. This property is acquired by a combination of thymic and extra-thymic mechanisms. We extend current models for the development of self/non-self discr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00360

    authors: Best K,Chain B,Watkins C

    更新日期:2015-08-07 00:00:00

  • Complement in the Initiation and Evolution of Rheumatoid Arthritis.

    abstract::The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01057

    authors: Holers VM,Banda NK

    更新日期:2018-05-28 00:00:00

  • Immunotherapeutic potential of extracellular vesicles.

    abstract::Extracellular vesicle or EV is a term that encompasses all classes of secreted lipid membrane vesicles. Despite being scientific novelties, EVs are gaining importance as a mediator of important physiological and pathological intercellular activities possibly through the transfer of their cargo of protein and RNA betwe...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00518

    authors: Zhang B,Yin Y,Lai RC,Lim SK

    更新日期:2014-10-22 00:00:00

  • How Mucosal Epithelia Deal with Stress: Role of NKG2D/NKG2D Ligands during Inflammation.

    abstract::Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01583

    authors: Antonangeli F,Soriani A,Cerboni C,Sciumè G,Santoni A

    更新日期:2017-11-20 00:00:00

  • Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease.

    abstract::The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00051

    authors: El-Zaatari M,Kao JY

    更新日期:2017-01-27 00:00:00

  • Nature vs. Nurture: Defining the Effects of Mesenchymal Stromal Cell Isolation and Culture Conditions on Resiliency to Palmitate Challenge.

    abstract::As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab ha...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01080

    authors: Boland LK,Burand AJ,Boyt DT,Dobroski H,Di L,Liszewski JN,Schrodt MV,Frazer MK,Santillan DA,Ankrum JA

    更新日期:2019-05-10 00:00:00

  • Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in Juvenile Influenza A Virus Infection.

    abstract::Influenza A virus (IAV) is a significant cause of life-threatening lower respiratory tract infections in children. Antiviral therapy is the mainstay of treatment, but its effectiveness in this age group has been questioned. In addition, damage inflicted on the lungs by the immune response to the virus may be as import...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00782

    authors: Coates BM,Staricha KL,Ravindran N,Koch CM,Cheng Y,Davis JM,Shumaker DK,Ridge KM

    更新日期:2017-07-10 00:00:00