Mature CD4 and CD8 T cells constitutively experience weak T cell receptor (TCR) stimulation in response to self-antigens, termed tonic (or basal) signaling. How tonic TCR signal strength impacts T cell responses to foreign antigens is an active area of investigation. Such studies rely on surrogate markers of tonic signal strength, including CD5, Ly6C, and transgenic reporters of Nr4a genes. Recent research indicates that strong tonic TCR signal strength influences basal T cell metabolism, effector differentiation, and TCR signal transduction. T cells that experience the strongest tonic TCR signaling exhibit features of T cell activation and negative regulation. These data suggest a model whereby adaptation to tonic signaling has lasting effects that alter T cell activation and differentiation.
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http://dx.doi.org/10.1016/j.coi.2021.09.007 | DOI Listing |
Brain Behav
January 2025
School of Psychology, University of Nottingham University Park, Nottingham, UK.
Background: Rhythmic median nerve stimulation (MNS) at 10 Hz has been shown to cause a substantial reduction in tic frequency in individuals with Tourette syndrome. The mechanism of action is currently unknown but is hypothesized to involve entrainment of oscillations within the sensorimotor cortex.
Objective: We used functional magnetic resonance spectroscopy (fMRS) to explore the dynamic effects of MNS on neurometabolite concentrations.
Chimeric antigen receptors (CAR) that mimic T cell receptors (TCR) on eliciting peptide-major histocompatibility complex (pMHC) specific T cell responses hold great promise in the development of immunotherapies against solid tumors, infections, and autoimmune diseases. However, broad applications of TCR-mimic (TCRm) CARs are hindered to date largely due to lack of a facile approach for the effective isolation of TCRm CARs. Here, we establish a highly efficient process for discovery of TCRm CARs from human naïve antibody repertories by combining recombinase-mediated large-diversity monoclonal library construction with T cell activation-based positive and negative screenings.
View Article and Find Full Text PDFJ Pain
November 2024
Department of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:
Sci Immunol
November 2024
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
During persistent antigen stimulation, exhausted CD8 T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway.
View Article and Find Full Text PDFJ Leukoc Biol
November 2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
The pre-T cell receptor (TCR) and TCR complexes are frequently expressed in T-cell acute lymphoblastic leukemia (T-ALL), an aggressive T cell precursor malignancy. Although mutations in TCR components are infrequent in T-ALL, earlier research indicated that transgenic αβ TCR expression in mouse T cell precursors promoted T-ALL development. However, we recently found that stimulation of TCR signaling in T-ALL induced leukemic cell apoptosis and suppressed leukemia.
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