68,107 results match your criteria human cd8

Role of nuclear localization in the regulation and function of T-bet and Eomes in exhausted CD8 T cells.

Cell Rep 2021 May;35(6):109120

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The transcription factors T-bet and Eomesodermin (Eomes) regulate CD8 T cell exhaustion through undefined mechanisms. Here, we show that the subcellular localization of T-bet and Eomes dictate their regulatory activity in exhausted T cells (Ts). Ts had a higher ratio of nuclear Eomes:T-bet than memory T cells (Ts) during chronic lymphocytic choriomeningitis virus (LCMV) infection in preclinical cancer models and in human tumors. Read More

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Spatiotemporal regulation of galectin-1-induced T-cell death in lamina propria from Crohn's disease and ulcerative colitis patients.

Apoptosis 2021 May 12. Epub 2021 May 12.

Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing intestinal inflammation. Galectin-1 (Gal-1) is an endogenous lectin with key pro-resolving roles, including induction of T-cell apoptosis and secretion of immunosuppressive cytokines. Despite considerable progress, the relevance of Gal-1-induced T-cell death in inflamed tissue from human IBD patients has not been ascertained. Read More

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Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity.

J Immunol Res 2021 21;2021:6654220. Epub 2021 Apr 21.

Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico.

Tuberculosis (TB), caused by (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. Read More

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The MNK1/2-eIF4E axis supports immune suppression and metastasis in postpartum breast cancer.

Cancer Res 2021 May 11. Epub 2021 May 11.

Goodman Cancer Research Center, McGill University.

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment has not been explored. Read More

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Expansion of GARP-Expressing CD4CD25FoxP3 T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa.

Virol Sin 2021 May 11. Epub 2021 May 11.

Centre for Cardio-Metabolic Research in Africa (CARMA), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, 7600, South Africa.

Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as persistent chronic inflammation, immune activation or exhaustion that can promote the onset of co-morbidities. As the exact function of regulatory T (Treg) cells in HIV remains unclear, this cross-sectional study investigated three expression markers (Forkhead box protein P3 [FOXP3], glycoprotein A repetitions predominant [GARP], special AT-rich sequence binding protein 1 [SATB1]) and compared their expansion between CD4CD25 and CD4CD25 T cells. Read More

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LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy.

J Exp Med 2021 Jul 11;218(7). Epub 2021 May 11.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Read More

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How COVID-19 Has Globalized: Unknown Origin, Rapid Transmission, and the Immune System Nourishment.

Adv Exp Med Biol 2021 ;1318:119-147

Research Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The novel coronavirus disease (COVID-19) profoundly influences T-cell immunity. The counts of total T cells and T-cell subsets, especially CD4+ and CD8+ T cells, are decreased in patients with COVID-19. Also, the function of these cells becomes less effective as the expression of immune inhibitory receptors, such as Tim3 and PD-1, increases over time during the disease. Read More

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Cellular and Humoral Immune Responses in Mice Immunized with Vaccinia Virus Expressing the SARS-CoV-2 Spike Protein.

J Immunol 2021 May 10. Epub 2021 May 10.

Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR;

The COVID-19 pandemic is a global health emergency, and the development of a successful vaccine will ultimately be required to prevent the continued spread and seasonal recurrence of this disease within the human population. However, very little is known about either the quality of the adaptive immune response or the viral Ag targets that will be necessary to prevent the spread of the infection. In this study, we generated recombinant Vaccinia virus expressing the full-length spike protein from SARS-CoV-2 (VacV-S) to evaluate the cellular and humoral immune response mounted against this viral Ag in mice. Read More

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Conserved and Novel Mouse CD8 T Cell Epitopes within SARS-CoV-2 Spike Receptor Binding Domain Protein Identified following Subunit Vaccination.

J Immunol 2021 May 10. Epub 2021 May 10.

Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO

The prior existence of human ACE2 protein-expressing mice used to study SARS-CoV and the rapid development of mouse-adapted virus strains have allowed the study of SARS-CoV-2 in mice, even as we are still learning about its natural pathology in humans. With myriad genetically altered strains on the C57BL/6 background and the abundance of immunological reagents available to interrogate its immune responses, the C57BL/6 mice may provide useful insight into the immunology of SARS-CoV-2 infection and vaccination. To conduct more detailed studies on their T cell responses to vaccines and infection, the epitopes eliciting those responses must be characterized in further detail. Read More

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Chlorogenic acid is a positive regulator of MDA5, TLR7 and NF-κB signaling pathways mediated antiviral responses against Gammacoronavirus infection.

Int Immunopharmacol 2021 May 7;96:107671. Epub 2021 May 7.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

Chlorogenic acid (CGA) is a phenolic compound that has been well studied for its antiviral, anti-inflammatory and immune stimulating properties. This research was aimed to focus on the antiviral properties of CGA on infectious bronchitis virus (IBV) in vivo and in vitro for the very first time. The outcome of in vitro experiments validated that, out of five previously reported antiviral components, CGA significantly reduced the relative mRNA expression of IBV-N in CEK cells. Read More

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Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV.

J Infect Dis 2021 May 10. Epub 2021 May 10.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: While social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general (1) and in the context of infectious disease, such as HIV (2,3). A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection.

Methods: To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n=35) and socially (n=41) housed SIV-infected pigtailed macaques (Macaca nemestrina). Read More

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Capturing T Lymphocytes' Dynamic Interactions With Human Neural Cells Using Time-Lapse Microscopy.

Front Immunol 2021 22;12:668483. Epub 2021 Apr 22.

Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.

To fully perform their functions, T lymphocytes migrate within organs' parenchyma and interact with local cells. Infiltration of T lymphocytes within the central nervous system (CNS) is associated with numerous neurodegenerative disorders. Nevertheless, how these immune cells communicate and respond to neural cells remains unresolved. Read More

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Small Molecule Cyclotriazadisulfonamide Abrogates the Upregulation of the Human Receptors CD4 and 4-1BB and Suppresses In Vitro Activation and Proliferation of T Lymphocytes.

Front Immunol 2021 21;12:650731. Epub 2021 Apr 21.

KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.

The small molecule cyclotriazadisulfonamide (CADA) down-modulates the human CD4 receptor, an important factor in T cell activation. Here, we addressed the immunosuppressive potential of CADA using different activation models. CADA inhibited lymphocyte proliferation with low cellular toxicity in a mixed lymphocyte reaction, and when human PBMCs were stimulated with CD3/CD28 beads, phytohemagglutinin or anti-CD3 antibodies. Read More

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Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy.

Breast Cancer Res 2021 May 10;23(1):51. Epub 2021 May 10.

Vascular Biology and Molecular Pathology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.

Background: Biglycan is a proteoglycan found in the extracellular matrix. We have previously shown that biglycan is secreted from tumor endothelial cells and induces tumor angiogenesis and metastasis. However, the function of stroma biglycan in breast cancer is still unclear. Read More

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Reduction of Graft-versus-Host-Disease in NOD.Cg-Prkdc Il2rg/SzJ (NSG) mice by co-transplantation of syngeneic human umbilical cord-derived mesenchymal stromal cells (UC-MSCs).

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.

Background: Graft-versus-Host Disease (GvHD) is one of the major complications following hematopoietic stem cell transplantation (HSCT), which remains the only curative therapy for many malignant diseases of the hematopoietic system. The immunomodulatory potential of mesenchymal stromal cells (MSCs) to treat GvHD is currently being tested in various preclinical and clinical trials.

Objectives: As the results of the preclinical and clinical trials on the use of MSCs to treat GvHD have not been consistent, we analyzed the potential beneficial effects of syngeneic versus allogenic treatment setting, culture expansion of the MSC and various MSC cell doses and time points of MSC transplantation in a murine GvHD model. Read More

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Delayed egress of CD8 T cells contributes to long-term pathology after ischemic stroke in male mice.

Brain Behav Immun 2021 May 5. Epub 2021 May 5.

Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, United States; Department of Neurology, Center for Advanced Translational Stroke Science, University of Kentucky, Lexington, Kentucky, USA. Electronic address:

Objective: Stroke is a debilitating disorder with significant annual mortality and morbidity rates worldwide. Immune cells are recruited to the injured brain within hours after stroke onset and can exhibit either protective or detrimental effects on recovery. However, immune cells, including CD8 T cells, persist in the injured brain for weeks, suggesting a longer-term role for the adaptive immune system during functional recovery. Read More

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Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis.

Cell 2021 Apr 30. Epub 2021 Apr 30.

Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA; Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA; Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, IL 60637, USA; University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA; Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA. Electronic address:

Cancer cell genetic variability and similarity to host cells have stymied development of broad anti-cancer therapeutics. Our innate immune system evolved to clear genetically diverse pathogens and limit host toxicity; however, whether/how innate immunity can produce similar effects in cancer is unknown. Here, we show that human, but not murine, neutrophils release catalytically active neutrophil elastase (ELANE) to kill many cancer cell types while sparing non-cancer cells. Read More

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Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Med Mol Morphol 2021 May 8. Epub 2021 May 8.

Department of Radiology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Read More

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Single-cell Transcriptomics Uncover a Novel Role of Myeloid Cells and T-lymphocytes in the Fibrotic Microenvironment in Peyronie's Disease.

Eur Urol Focus 2021 May 4. Epub 2021 May 4.

Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Background: Peyronie's disease (PD) is an acquired fibrotic disease affecting the penile tunica albuginea that can lead to curvature and deformities, shortening, and erectile dysfunction. Although immunological mechanisms have been suggested for the pathophysiology of PD, these have not been investigated using single-cell transcriptomics.

Objective: To investigate the immunological signature of plaques from PD patients using immunohistochemistry (IHC) and single-cell RNA sequencing (scRNA-Seq). Read More

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Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma.

Eur J Cancer 2021 May 4;151:25-34. Epub 2021 May 4.

Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, CT, USA. Electronic address:

Objective: The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome affects immunity in human cancer. Read More

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Resolution of hepatitis E virus infection in CD8+ T cell depleted rhesus macaques.

J Hepatol 2021 May 4. Epub 2021 May 4.

Center for Vaccines and Immunity, The Research Institute at Nationwide Children's, 700 Children's Drive, Columbus, OH, USA; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA. Electronic address:

Background And Aim: HEV is a significant cause of acute hepatitis globally. Some genotypes establish persistent infection when immunity is impaired. Adaptive immune mechanisms that mediate resolution of infection have not been identified. Read More

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Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer.

Stem Cell Reports 2021 May 5. Epub 2021 May 5.

Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA. Electronic address:

Induced pluripotent stem cells (iPSCs) and cancer cells share cellular similarities and transcriptomic profiles. Here, we show that an iPSC-based cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8 T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4 T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma (PDAC) mice. We demonstrate that shared gene expression profiles of "iPSC-cancer signature genes" and others are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. Read More

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Hepatitis C Virus Relapse After Ultrashort Direct-Acting Antiviral Therapy Associates With Expression of Genes Involved With Natural Killer-Cell and CD8 T-Cell Function.

Open Forum Infect Dis 2021 Apr 13;8(4):ofab118. Epub 2021 Mar 13.

Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, USA.

To identify immunologic correlates of hepatitis C virus (HCV) relapse after direct-acting antiviral (DAA) therapy, we quantified select immune transcripts in whole blood from noncirrhotic HCV subjects treated with 4-6 weeks of DAAs. We identified specific markers of natural killer-cell and CD8 T-cell function (, , ) with higher expression in subjects who relapsed. These findings suggest a role for host immunity in HCV eradication with ultrashort DAA therapy. Read More

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Corrigendum: Expression of Human Epidermal Growth Factor Receptor-2 Status and Programmed Cell Death Protein-1 Ligand Is Associated With Prognosis in Gastric Cancer.

Front Oncol 2021 20;11:672599. Epub 2021 Apr 20.

Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2020. Read More

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Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status.

World J Clin Oncol 2021 Apr;12(4):238-248

Department of Immunology and Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney 2000, NSW, Australia.

Background: Recent studies in non-colorectal malignancy have associated T resident memory (T) cells with improved patient survival. It is unknown if T plays a role in colorectal cancer (CRC).

Aim: To examine the potential role of T cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status. Read More

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Vaccine Inoculation Route Modulates Early Immunity and Consequently Antigen-Specific Immune Response.

Front Immunol 2021 20;12:645210. Epub 2021 Apr 20.

UMR1184 IMVA-HB, IDMIT Department, Université Paris-Saclay - INSERM U1184 - CEA, Fontenay-aux-Roses, France.

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. Read More

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Single-Cell TCR Sequencing Reveals the Dynamics of T Cell Repertoire Profiling During Infection.

Front Microbiol 2021 20;12:637500. Epub 2021 Apr 20.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

T cell responses play critical roles in host adaptive immunity against . However, the dynamics and diversity of the T cell immune repertoire in human immunodeficiency virus (HIV)-negative pneumonia (PCP) remains unclear. In this study, single-cell RNA and single-cell T cell receptor (TCR) sequencing were applied to cells sorted from lung tissues of mice infected with . Read More

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A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer.

Nat Med 2021 May 6. Epub 2021 May 6.

Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.

Immune-checkpoint blockade (ICB) combined with neoadjuvant chemotherapy improves pathological complete response in breast cancer. To understand why only a subset of tumors respond to ICB, patients with hormone receptor-positive or triple-negative breast cancer were treated with anti-PD1 before surgery. Paired pre- versus on-treatment biopsies from treatment-naive patients receiving anti-PD1 (n = 29) or patients receiving neoadjuvant chemotherapy before anti-PD1 (n = 11) were subjected to single-cell transcriptome, T cell receptor and proteome profiling. Read More

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LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy.

Nat Cell Biol 2021 May 6. Epub 2021 May 6.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8 T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Read More

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Steroid hormone bioavailability is controlled by the lymphatic system.

Sci Rep 2021 May 6;11(1):9666. Epub 2021 May 6.

Department of Nephrology and Hypertension, University of Bern, 3010, Bern, Switzerland.

The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Read More

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