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doi:10.22028/D291-45916
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 |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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ijms-26-07024.pdf | 11,57 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons