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T cell age

Young-Mee Kim, Seock-Won Youn, Varadarajan Sudhahar, Archita Das, Reyhaan Chandhri, Henar Cuervo Grajal, Junghun Kweon, Silvia Leanhart, Lianying He, Peter T Toth, Jan Kitajewski, Jalees Rehman, Yisang Yoon, Jaehyung Cho, Tohru Fukai, Masuko Ushio-Fukai
Mitochondrial dynamics are tightly controlled by fusion and fission, and their dysregulation and excess reactive oxygen species (ROS) contribute to endothelial cell (EC) dysfunction. How redox signals regulate coupling between mitochondrial dynamics and endothelial (dys)function remains unknown. Here, we identify protein disulfide isomerase A1 (PDIA1) as a thiol reductase for the mitochondrial fission protein Drp1. A biotin-labeled Cys-OH trapping probe and rescue experiments reveal that PDIA1 depletion in ECs induces sulfenylation of Drp1 at Cys644 , promoting mitochondrial fragmentation and ROS elevation without inducing ER stress, which drives EC senescence...
June 19, 2018: Cell Reports
Kylie M Quinn, Annette Fox, Kim L Harland, Brendan E Russ, Jasmine Li, Thi H O Nguyen, Liyen Loh, Moshe Olshanksy, Haroon Naeem, Kirill Tsyganov, Florian Wiede, Rosela Webster, Chantelle Blyth, Xavier Y X Sng, Tony Tiganis, David Powell, Peter C Doherty, Stephen J Turner, Katherine Kedzierska, Nicole L La Gruta
Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (TVM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TN cells) retain proliferative capacity in both aged mice and humans...
June 19, 2018: Cell Reports
Hung Cao Dinh, Ivan Bautmans, Ingo Beyer, Tony Mets, Oscar Okwudiri Onyema, Louis Nuvagah Forti, Wim Renmans, Sam Vander Meeren, Kristin Jochmans, Sofie Vermeiren, Roberta Vella Azzopardi, Rose Njemini
Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immuno-senescence (IS) - predominantly driven by cytomegalovirus (CMV) - has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty...
June 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Ankita Singh, Prateek Bhatia, Amita Trehan, Deepak Bansal, Ajit Singh, Alka Bhatia
Background & objectives: Significance of apoptosis as a prognostic marker is less well studied in paediatric acute lymphoblastic leukaemia (ALL) cases. Hence, a prospective study, involving 30 paediatric ALL cases, was done to assess the clinical relevance of in vivo apoptosis. Methods: Peripheral blood mononuclear cells from all patients were subjected to annexin V/propidium iodide staining to detect the degree of apoptosis [apoptotic index (AI)] at day 0 and day 35 post-induction chemotherapy...
March 2018: Indian Journal of Medical Research
Tim R de Back, Arnon P Kater, Sanne H Tonino
Chronic lymphocytic leukemia (CLL) is frequently complicated by cytopenias, either due to bone marrow infiltration or autoimmunity, resulting in autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA) or autoimmune neutropenia (AIN). Morbidity due to autoimmune cytopenias (AIC) can be substantial; in addition, infection risk increases and pre-existing infections might deteriorate due to immunosuppressive medication. In the aging population, CLL occurs more frequently and AIC related to CLL represent a growing clinical challenge...
June 20, 2018: Expert Review of Hematology
Adam J de Smith, Kyle M Walsh, Stephen S Francis, Chenan Zhang, Helen M Hansen, Ivan Smirnov, Libby Morimoto, Todd P Whitehead, Alice Kang, Xiaorong Shao, Lisa F Barcellos, Roberta McKean-Cowdin, Luoping Zhang, Cecilia Fu, Rong Wang, Herbert Yu, Josephine Hoh, Andrew T Dewan, Catherine Metayer, Xiaomei Ma, Joseph L Wiemels
Genome-wide association studies of childhood acute lymphoblastic leukemia (ALL) have identified regions of association at PIP4K2A and upstream of BMI1 at chromosome 10p12.31-12.2. The contribution of both loci to ALL risk and underlying functional variants remain to be elucidated. We carried out single nucleotide polymorphism (SNP) imputation across chromosome 10p12.31-12.2 in Latino and non-Latino white ALL cases and controls from two independent California childhood leukemia studies, and additional Genetic Epidemiology Research on Aging study controls...
June 19, 2018: International Journal of Cancer. Journal International du Cancer
Veronica Mugarab Samedi, Amy Shafey, Essa Al Awad, Luis Murguia Favela
Healthy looking newborns may have severe combined immunodeficiency (SCID), and neonatologists frequently are the first physicians to encounter these patients. Physicians usually have a high index of suspicion for this condition in presence of certain risk factors (unexplained infants' deaths, consanguinity); however, >80% of infants with SCID have no positive family history. A timely diagnosis of this condition is crucial in decreasing both mortality and morbidity. The only way to detect SCID prior to the onset of infections is newborn screening (NBS)...
April 2018: American Journal of Perinatology Reports
A Sanghani-Kerai, L Osagie-Clouard, G Blunn, M Coathup
Objectives: This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods: Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats...
April 2018: Bone & Joint Research
Jorgen Thorup, Erik Clasen-Linde, Lihua Dong, Simone Hildorf, Stine Gry Kristensen, Claus Yding Andersen, Dina Cortes
Introduction: Orchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk. Materials and methods: We included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old...
2018: Frontiers in Endocrinology
Z X Hu, W N Song, X D Lu, M L Zhou, J H Shao
This study aimed to evaluate the efficacy of T-cell immune function and L-dopamine (L-DOPA) in patients with Parkinson’s disease (PD). Sixty subjects (included in the study group) with PD who were patients of the Neurology Department of The Affiliated Hospital of Hangzhou Normal University from July 2015 to March 2017 were selected. The study group was then categorized into groups according to the age of the patients, severity of disease, level of cognition, and treatment of L-DOPA. The control group (30 cases) was from the healthy population of the check-up center at The Affiliated Hospital of Hangzhou Normal University...
May 2018: Journal of Biological Regulators and Homeostatic Agents
Anthony P Y Liu, Pamela P W Lee, Janette S Y Kwok, Rock Y Y Leung, Alan K S Chiang, Shau-Yin Ha, Daniel K L Cheuk, Godfrey C F Chan
Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2...
June 19, 2018: Pediatric Transplantation
D Roumanes, A R Falsey, S Quataert, S Secor-Socha, F E-H Lee, H Yang, S Bandyopadhyay, J Holden-Wiltse, D J Topham, E E Walsh
Background: The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum. Methods: Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry. Results: There were no significant age-related differences in frequency of CD4+ T cells synthesizing interferon (IFN)γ, interleukin (IL)2, IL4, IL10, or tumor necrosis factor (TNF)α or in CD8+IFNγ+ T cells...
June 16, 2018: Journal of Infectious Diseases
K Olek-Hrab, J Maj, E Chmielowska, A Jankowska-Konsur, B Olszewska, B Kręcisz, P Iwankowski, M Mackiewicz-Wysocka, Z Adamski, R Nowicki, M Sokolowska-Wojdylo
OBJECTIVE: The first report concerning methotrexate (MTX) in the treatment of Mycosis fungoides (MF) was published in 1964 by Wright. The mechanism of MTX action in the treatment of primary cutaneous T-cell lymphoma (CTCL) has been not explained in detail yet (the anti-inflammatory, immunomodulating, immunosuppressive, and cytostatic actions have been under discussion). PATIENTS AND METHODS: This is a retrospective analysis of 79 MF patients in 4 dermatology clinical centers in Poland...
June 2018: European Review for Medical and Pharmacological Sciences
Yanping Zhang, Shi Ding, Jie Yang, Xingfeng Chen, Weilin Huang
There is emerging evidence that some microRNAs can promote or suppress several human cancer development and progression. However, the profile and molecular mechanism of microRNAs for human breast cancer is poorly unknown. We used bioinformatics approaches to find new candidate diagnostic and therapeutic miRNAs in human breast cancer via analysis of TCGA RNA sequencing data and publicly GEO microarray data, in order to provide theoretical basis for the future investigations of breast cancer. Decreased expression miR-146a was identified as a key regulator of human breast cancer development and progression...
June 18, 2018: Pathology Oncology Research: POR
Timo Jan Oberstein, Lava Taha, Philipp Spitzer, Janina Hellstern, Martin Herrmann, Johannes Kornhuber, Juan Manuel Maler
The neuropathological hallmarks of Alzheimer's disease (AD), i.e., neuritic plaques and neurofibrillary tangles, consist of beta amyloid peptides (Aβ) and hyperphosphorylated Tau. These are accompanied by reactive microglia and astrocytes in the vicinity of the neuritic plaques and by changes to the peripheral immune system, e.g., an increase of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in the peripheral blood. To address a potential involvement of peripheral T helper cell (Th ) subsets in AD, we conducted a case control study with 54 individuals with AD dementia ( n  = 14), with mild cognitive impairment (MCI) due to AD (MCIAD , n  = 14), with MCI unlikely due to AD (MCIother , n  = 13), and controls without cognitive impairment (controls, n  = 13)...
2018: Frontiers in Immunology
Stella Lukas Yani, Michael Keller, Franz Leonard Melzer, Birgit Weinberger, Luca Pangrazzi, Sieghart Sopper, Klemens Trieb, Monia Lobina, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Beatrix Grubeck-Loebenstein
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...
2018: Frontiers in Immunology
Aneta Monika Gawlik, Elzbieta Berdej-Szczot, Dorota Blat, Renata Klekotka, Tomasz Gawlik, Ewa Blaszczyk, Magdalena Hankus, Ewa Malecka-Tendera
Objective: The risk of autoimmune diseases (AD) in patients with Turner Syndrome (TS) is twice higher than in the general female population and four times higher than in the male population. The causes of the increased incidence of AD in TS are still under discussion. We hypothesized the presence of a specific humoral, cellular, and regulatory T cell (Treg) immunity profile which predisposes to AD, disorders of immunity, and disorders of immune regulation. Methods: The study encompassed 37 girls with TS and with no signs of infection...
2018: Frontiers in Endocrinology
Songtao An, Xiaoyin Wang, Melissa A Ruck, Hilda J Rodriguez, Dmitry S Kostyushev, Monika Varga, Emmy Luu, Ronak Derakhshandeh, Sergey V Suchkov, Scott C Kogan, Michelle L Hermiston, Matthew L Springer
Treatment of myocardial infarction (MI) with bone marrow cells (BMCs) improves post-MI cardiac function in rodents. However, clinical trials of BMC therapy have been less effective. While most rodent experiments use young healthy donors, patients undergoing autologous cell therapy are older and post-MI. We previously demonstrated that BMCs from aged and post-MI donor mice are therapeutically impaired, and that donor MI induces inflammatory changes in BMC composition including reduced levels of B lymphocytes...
June 15, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Roxane Boivin, Amandine Vargas, Patricia Cano, Jean-Pierre Lavoie
Recurrent inflammation in severe equine asthma causes a remodeling of the airways leading to incompletely reversible airway obstruction. Despite the improvement of clinical signs and lung function with glucocorticoids (GC), inflammation, translated by an increased percentage of neutrophils, persists in the airways. Regulatory T cells (Treg) have been shown to have anti-inflammatory properties and play an important role in balancing the immune response by suppressing effector lymphocyte activity. However, interactions between Treg, neutrophils and glucocorticosteroids in vivo are unclear, particularly in asthma...
July 2018: Veterinary Immunology and Immunopathology
Joaquin T Valderrama, Elizabeth Francis Beach, Ingrid Yeend, Mridula Sharma, Bram Van Dun, Harvey Dillon
Recent animal studies have shown that the synapses between inner hair cells and the dendrites of the spiral ganglion cells they innervate are the elements in the cochlea most vulnerable to excessive noise exposure. Particularly in rodents, several studies have concluded that exposure to high level octave-band noise for 2 h leads to an irreversible loss of around 50% of synaptic ribbons, leaving audiometric hearing thresholds unaltered. Cochlear synaptopathy following noise exposure is hypothesized to degrade the neural encoding of sounds at the subcortical level, which would help explain certain listening-in-noise difficulties reported by some subjects with otherwise 'normal' hearing...
June 12, 2018: Hearing Research
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