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Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies.
Front Immunol
January 2025
School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Introduction: The high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon.
Methods: We performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear cell (PBMC) samples from Omicron infection and naïve with booster vaccination.
Results: We found that after breakthrough infection, multiple cell clusters showed activation of the type I IFN pathway and widespread expression of Interferon-stimulated genes (ISGs); T and B lymphocytes exhibited antiviral and proinflammatory-related differentiation features with pseudo-time trajectories; and large TCR clonal expansions were concentrated in effector CD8 T cells, and clonal expansions of BCRs showed a preference for IGHV3.
Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation.
Gut
January 2025
Division of Clinical Microbiology,Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden
Background: Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy.
Objective: We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment.
Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.
Nat Commun
January 2025
Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.
View Article and Find Full Text PDFSpecific selection of stimulation-responsive γδ T-cells utilizing a short-term activation assay.
Methods Cell Biol
January 2025
Institute of Immunology, Christian-Albrechts University and University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany. Electronic address:
T cells expressing the γδ T-cell receptor (TCR) represent a numerically small proportion of total T cells. Unlike αβ T cells they are activated by non-peptide antigens independently of MHC-presentation. γδ T cells have been recognized as a favorable prognostic marker across different tumor entities.
View Article and Find Full Text PDFCigarette smoke components modulate the MR1-MAIT axis.
J Exp Med
February 2025
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Tobacco smoking is prevalent across the world and causes numerous diseases. Cigarette smoke (CS) compromises immunity, yet little is known of the components of CS that impact T cell function. MR1 is a ubiquitous molecule that presents bacterial metabolites to MAIT cells, which are highly abundant in the lungs.
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