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Titel: IFNγ Expression Correlates with Enhanced Cytotoxicity in CD8+ T Cells
VerfasserIn: Pattu, Varsha
Krause, Elmar
Chang, Hsin-Fang
Rettig, Jens
Li, Xuemei
Sprache: Englisch
Titel: International Journal of Molecular Sciences
Bandnummer: 26
Heft: 14
Verlag/Plattform: MDPI
Erscheinungsjahr: 2025
Freie Schlagwörter: CD8+ T cells
interferon-gamma
CD107a
cytotoxicity
subcellular localization
CRTAM
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: CD8+ T lymphocytes (CTLs) act as serial killers of infected or malignant cells by releasing large amounts of interferon-gamma (IFNγ) and granzymes. Although IFNγ is a pleiotropic cytokine with diverse immunomodulatory functions, its precise spatiotemporal regulation and role in CTL-mediated cytotoxicity remain incompletely understood. Using wild-type and granzyme B-mTFP knock-in mice, we employed a combination of in vitro approaches, including T cell isolation and culture, plate-bound anti-CD3e stimulation, degranulation assays, flow cytometry, immunofluorescence, and structured illumination microscopy, to investigate IFNγ dynamics in CTLs. IFNγ expression in CTLs was rapid, transient, and strictly dependent on T cell receptor (TCR) activation. We identified two functionally distinct IFNγ-producing subsets: IFNγ high (IFNγ hi) and IFNγ low (IFNγ lo) CTLs. IFNγ hi CTLs exhibited an effector/effector memory phenotype, significantly elevated CD107a surface expression (a marker of lytic granule exocytosis), and higher colocalization with cis-Golgi and granzyme B compared to IFNγ lo CTLs. Furthermore, CRTAM, an early activation marker, correlated with IFNγ expression in naive CTLs. Our findings establish a link between elevated IFNγ production and enhanced CTL cytotoxicity, implicating CRTAM as a potential regulator of early CTL activation and IFNγ induction. These insights provide a foundation for optimizing T cell-based immunotherapies against infections and cancers.
DOI der Erstveröffentlichung: 10.3390/ijms26147024
URL der Erstveröffentlichung: https://doi.org/10.3390/ijms26147024
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-459167
hdl:20.500.11880/40305
http://dx.doi.org/10.22028/D291-45916
ISSN: 1422-0067
Datum des Eintrags: 29-Jul-2025
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/article/10.3390/ijms26147024/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Physiologie
Professur: M - Prof. Dr. Jens Rettig
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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