339,997 results match your criteria human t-cell

Strongyloides stercoralis and HTLV-1 coinfection in CD34+ cord blood stem cell humanized mice: Alteration of cytokine responses and enhancement of larval growth.

PLoS Negl Trop Dis 2021 Jul 27;15(7):e0009559. Epub 2021 Jul 27.

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 and Strongyloides stercoralis are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and S. Read More

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Coreceptor therapy has distinct short- and long-term tolerogenic effects intrinsic to autoreactive effector T cells.

JCI Insight 2021 Jul 27. Epub 2021 Jul 27.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United States of America.

Immunotherapies are needed in the clinic that effectively suppress beta cell autoimmunity and reestablish long-term self-tolerance in type 1 diabetes. We previously demonstrated that nondepleting αCD4 and αCD8α antibodies establish rapid and indefinite remission in recent-onset diabetic NOD mice. Diabetes reversal by coreceptor therapy (CoRT) is induced by suppression of pathogenic effector T cells (Teff) and the selective egress of T cells from the pancreatic lymph nodes and islets that remain free of infiltration long-term. Read More

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A novel recombinant protein vaccine containing the different E7 proteins of the HPV16, 18, 6, 11 E7 linked to the HIV-1 Tat (47-57) improve cytotoxic immune responses.

Biotechnol Lett 2021 Jul 27. Epub 2021 Jul 27.

Department of Microbiology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Objectives: Human papillomavirus infection (HPV) is the most common viral infection which is causes of cervical, penal, vulvar, anal and, oropharyngeal cancer. E7 protein of HPV is a suitable target for induction of T cell responses and controlling HPV-related cancer. The aim of the current study was to designed and evaluated a novel fusion protein containing the different E7 proteins of the HPV 16, 18, 6 and 11, linked to the cell-penetrating peptide HIV-1 Tat 49-57, in order to improve cytotoxic immune responses in in-vitro and in-vivo. Read More

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Calmodulin Antagonist W-7 Enhances Intermediate Conductance Ca- Sensitive Basolateral Potassium Channel (IK) Activity in Human Colonic Crypts.

J Membr Biol 2021 Jul 27. Epub 2021 Jul 27.

Leeds Institute of Medical Research at St James, St James University Hospital, Beckett Street, Leeds, LS9 7TF, UK.

Intermediate conductance potassium (IK) channels are exquisitively Ca sensitive, intracellular Ca regulating channel activity by complexing with calmodulin (CaM), which is bound to the cytosolic carboxyl tail. Although CaM antagonists might be expected to decrease IK channel activity, the effect of W-7 in human T lymphocytes are conflicting. We therefore evaluated the effect of W-7 on basolateral IK channels in human colonic crypt cells. Read More

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Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models.

MAbs 2021 Jan-Dec;13(1):1954136

External Innovations, IPSEN, Cambridge, MA, USA.

Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. Read More

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T cell stiffness is enhanced upon formation of immunological synapse.

Elife 2021 Jul 27;10. Epub 2021 Jul 27.

Biophysics, Saarland University, Homburg, Germany.

T cells are activated by target cells via an intimate contact, termed immunological synapse (IS). Cellular mechanical properties, especially stiffness, are essential to regulate cell functions. However, T cell stiffness at a subcellular level at the IS still remains largely elusive. Read More

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Cognitive frailty predicting death and disability in Chinese elderly.

Neurol Res 2021 Jul 27:1-9. Epub 2021 Jul 27.

Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

: Although multiple sclerosis (MS) is known to be an immune-mediated disease, very little is known about its etiopathogenesis. MicroRNAs (miRNAs) are small non-coding proteins involved in the regulation of gene expression. T-cell activation potential in neurodegenerative diseases has been a research topic of interest in recent years Cytokines play an important role in the course and pathogenesis of MS, The aim of the present study was to analyze expression levels of miR-20, miR-21, miR-26, miR-155, and Let-7, which target the cytokines interleukin IL-17 and IL-23, in order to evaluate the relationship between MS and miRNAs that modulate the expression of cytokines involved in the autoimmune pathway. Read More

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CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.

Nat Med 2021 Jul 26. Epub 2021 Jul 26.

Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.

Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. Read More

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Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4 T cell identity and function.

Nat Immunol 2021 Aug 26;22(8):969-982. Epub 2021 Jul 26.

Blood Cell Development and Cancer, Fox Chase Cancer Center, Philadelphia, PA, USA.

The transcription factor ThPOK (encoded by the Zbtb7b gene) controls homeostasis and differentiation of mature helper T cells, while opposing their differentiation to CD4 intraepithelial lymphocytes (IELs) in the intestinal mucosa. Thus CD4 IEL differentiation requires ThPOK transcriptional repression via reactivation of the ThPOK transcriptional silencer element (Sil). In the present study, we describe a new autoregulatory loop whereby ThPOK binds to the Sil to maintain its own long-term expression in CD4 T cells. Read More

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Epigenetic scars of CD8 T cell exhaustion persist after cure of chronic infection in humans.

Nat Immunol 2021 Aug 26;22(8):1020-1029. Epub 2021 Jul 26.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8 T cells acquire a distinct epigenetic state, but it is not known whether that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we show that the epigenetic state of exhaustion is largely irreversible, even after curative therapy. Read More

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Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.

Nat Immunol 2021 Aug 26;22(8):1008-1019. Epub 2021 Jul 26.

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.

Exhausted CD8 T cells (T) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate T cells, but reinvigoration is not durable. A major unanswered question is whether T cells differentiate into functional durable memory T cells (T) upon antigen clearance. Read More

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Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory.

Nat Immunol 2021 Aug 26;22(8):1030-1041. Epub 2021 Jul 26.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Here we confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8 T cells in human hepatitis C virus (HCV) infection before and after treatment. Read More

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Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.

Nat Commun 2021 07 26;12(1):4515. Epub 2021 Jul 26.

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. Read More

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PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", 20122 Milan, Italy;

Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5 to PtdIns(4,5) They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Read More

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Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques.

mBio 2021 Jul 27:e0150321. Epub 2021 Jul 27.

Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseasesgrid.419681.3, National Institutes of Health, Hamilton, Montana, USA.

Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted of either CD4, CD8, or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to that in controls. Read More

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A graph centrality-based approach for candidate gene prediction for type 1 diabetes.

Immunol Res 2021 Jul 23. Epub 2021 Jul 23.

School of Physics, University of Hyderabad, Gachibowli, Hyderabad, 500046, Telangana, India.

Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes is an autoimmune disease that may pose life-threatening situations to individuals. In most cases, cytotoxic T lymphocytes (CTLs) promotes killing of islets of Langerhans in the pancreas, which harbour insulin-producing beta cells. The trigger for autoimmune attack is still unclear; therefore, identifying and targeting candidate genes are imperative to hinder its deleterious effects. Read More

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Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

Br J Cancer 2021 Jul 22. Epub 2021 Jul 22.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. Read More

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EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC).

Stem Cell Res Ther 2021 Jul 22;12(1):419. Epub 2021 Jul 22.

INSERM UA9, University Paris-Saclay, 94800, Villejuif, France.

Background: During aging, hematopoietic stem cells (HSC) lose progressively both their self-renewal and differentiation potential. The precise molecular mechanisms of this phenomenon are not well established. To uncover the molecular events underlying this event, we have performed a bioinformatics analysis of 650 single-cell transcriptomes. Read More

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MicroRNA-based host response to toxicant exposure is influenced by the presence of gut microbial populations.

Sci Total Environ 2021 Jul 20;797:149130. Epub 2021 Jul 20.

Center for Microbial Ecology, Michigan State University, East Lansing, MI 48824, USA; Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, MI 48824, USA; Department of Civil and Environmental Engineering, East Lansing, MI 48824, USA. Electronic address:

Segmented filamentous bacteria (SFB) and Bacteroides fragilis are known to interact with the host immune response through the aryl hydrocarbon receptor (Ahr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental toxicant and a high-affinity Ahr ligand has the potential to modify the effect of SFB and B. fragilis. Read More

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pre-erythrocytic vaccine antigens enhance sterile protection in mice induced by circumsporozoite protein.

Infect Immun 2021 Jul 26:IAI0016521. Epub 2021 Jul 26.

Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Pre-erythrocytic vaccines prevent malaria by targeting parasites in the clinically silent sporozoite and liver stages and preventing progression to the virulent blood stages. The leading pre-erythrocytic vaccine RTS,S/AS01E (Mosquirix®) entered implementation programs in 2019 and targets the major sporozoite surface antigen called circumsporozoite protein or CSP. However, in phase III clinical trials, RTS,S conferred partial protection with limited durability, indicating a need to improve CSP-based vaccination. Read More

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Immunogenicity and efficacy of live-attenuated murium vaccine candidate CVD 1926 in a rhesus macaque model of gastroenteritis.

Infect Immun 2021 Jul 26:IAI0008721. Epub 2021 Jul 26.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

murium are a common cause of food-borne gastroenteritis, and a less frequent but important cause of invasive disease, especially in developing countries. In our previous work, we showed that a live-attenuated murium vaccine (CVD 1921) was safe and immunogenic in rhesus macaques, although shed for an unacceptably long period (10 days) post-immunization. Consequently, we engineered a new strain, CVD 1926, which was shown to be safe and immunogenic in mice, as well as less reactogenic in mice and human cell-derived organoids than CVD 1921. Read More

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Molecular mismatch predicts T cell mediated rejection and de novo donor specific antibody formation after living-donor liver transplantation.

Liver Transpl 2021 Jul 26. Epub 2021 Jul 26.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation, compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplant recipients. A retrospective observational study of 45 living-donor liver transplantations was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. Read More

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Know thy immune self & non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.

Proteomics 2021 Jul 26:e2000143. Epub 2021 Jul 26.

Centre for Cellular and Molecular Physiology, Wellcome Centre for Human Genetics & Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

T cells play an important role in the adaptive immune response to a variety of infections and cancers. Initiation of a T cell mediated immune response requires antigen recognition in a process termed MHC (Major Histocompatibility Complex) restriction. A T cell antigen is a composite structure made up of a peptide fragment bound within the antigen-binding groove of an MHC-encoded class I or class II molecule. Read More

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Low oxygen-levels decrease adaptive immune responses and ameliorate experimental asthma in mice.

Allergy 2021 Jul 26. Epub 2021 Jul 26.

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.

Background: High altitude therapy has been used as add-on treatment for allergic asthma with considerable success. However, the underlying mechanisms remain unclear. In order to investigate the possible therapeutic effects of high altitude therapy on allergic asthma, we utilised a new in vivo mouse model. Read More

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A Preclinical Human-Derived Autologous Gastric Cancer Organoid/Immune Cell Co-Culture Model to Predict the Efficacy of Targeted Therapies.

J Vis Exp 2021 Jul 6(173). Epub 2021 Jul 6.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson;

Tumors expressing programmed cell death-ligand 1 (PD-L1) interact with programmed cell death protein 1 (PD-1) on CD8+ cytotoxic T lymphocytes (CTLs) to evade immune surveillance leading to the inhibition of CTL proliferation, survival, and effector function, and subsequently cancer persistence. Approximately 40% of gastric cancers express PD-L1, yet the response rate to immunotherapy is only 30%. We present the use of human-derived autologous gastric cancer organoid/immune cell co-culture as a preclinical model that may predict the efficacy of targeted therapies to improve the outcome of cancer patients. Read More

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Consequences of hemophagocytic lymphohistiocytosis-like cytokine release syndrome toxicities and concurrent bacteremia.

Pediatr Blood Cancer 2021 Jul 26:e29247. Epub 2021 Jul 26.

Pediatric Oncology Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.

Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Read More

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Naïve T Cell Quiescence in Immune Aging.

Adv Geriatr Med Res 2021 26;3(3). Epub 2021 Jun 26.

Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94304, USA.

Naïve T cells are critical for protection against emerging viral and bacterial infections. However, the ability of these cells to elicit effective long-term immune responses declines with age and contributes to increased disease susceptibility in older individuals. This decline has been linked with the breakdown of cellular quiescence that causes partial differentiation of naïve T cells with age, but the underlying mediators of this breakdown are unclear. Read More

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Human hepatitis D virus-specific T cell epitopes.

JHEP Rep 2021 Aug 23;3(4):100294. Epub 2021 Apr 23.

I. Medical Department (Gastroenterology with the Sections Infectiology and Tropical Medicine), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

HDV is a small, defective RNA virus that requires the HBsAg of HBV for its assembly, release, and transmission. Chronic HBV/HDV infection often has a severe clinical outcome and is difficult to treat. The important role of a robust virus-specific T cell response for natural viral control has been established for many other chronic viral infections, but the exact role of the T cell response in the control and progression of chronic HDV infection is far less clear. Read More

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KDM1A Promotes Immunosuppression in Hepatocellular Carcinoma by Regulating PD-L1 through Demethylating MEF2D.

J Immunol Res 2021 1;2021:9965099. Epub 2021 Jul 1.

Department of Gastroenterology, Jingmen No. 1 People's Hospital, 168 Xiangshan Road, Jingmen 448000, China.

Background: Immune checkpoint inhibitor therapy targeting antiprogrammed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is effective in the treatment of some hepatocellular carcinomas (HCC). Hence, further identification of biological targets related to PD-L1 regulation in HCC is beneficial to improve the clinical efficacy of immunotherapy. Some HCC cells express lysine-specific demethylase 1A (KDM1A), which is implicated in the reduced survival time of patients. Read More

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Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer.

Front Mol Biosci 2021 9;8:686803. Epub 2021 Jul 9.

Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine,Tongji University, Shanghai, China.

Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified. The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. Read More

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