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Titel: Faster cytotoxicity with age : Increased perforin and granzyme levels in cytotoxic CD8+ T cells boost cancer cell elimination
VerfasserIn: Zöphel, Dorina
Angenendt, Adrian
Kaschek, Lea
Ravichandran, Keerthana
Hof, Chantal
Janku, Sandra
Hoth, Markus
Lis, Annette
Sprache: Englisch
Titel: Aging Cell
Bandnummer: 21
Heft: 8
Verlag/Plattform: Wiley
Erscheinungsjahr: 2022
Freie Schlagwörter: aging
CD8+ T cells
CTL
cytotoxicity
granzyme
immunosenescence
perforin
tumor immunology
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: A variety of intrinsic and extrinsic factors contribute to the altered efficiency of CTLs in elderly organisms. In particular, the efficacy of antiviral CD8+ T cells responses in the elderly has come back into focus since the COVID-19 pandemic outbreak. However, the exact molecular mechanisms leading to alterations in T cell function and the origin of the observed impairments have not been fully explored. Therefore, we investigated whether intrinsic changes affect the cytotoxic ability of CD8+ T cells in aging. We focused on the different subpopulations and time-resolved quantification of cytotoxicity during tumor cell elimination. We report a surprising result: Killing kinetics of CD8+ T cells from elderly mice are much faster than those of CD8+ T cells from adult mice. This is true not only in the total CD8+ T cell population but also for their effector (TEM) and central memory (TCM) T cell subpopulations. TIRF experiments reveal that CD8+ T cells from elderly mice possess comparable numbers of fusion events per cell, but significantly increased numbers of cells with granule fusion. Analysis of the cytotoxic granule (CG) content shows significantly increased perforin and granzyme levels and turns CD8+ T cells of elderly mice into very efficient killers. This highlights the importance of distinguishing between cell-intrinsic alterations and microenvironmental changes in elderly individuals. Our results also stress the importance of analyzing the dynamics of CTL cytotoxicity against cancer cells because, with a simple endpoint lysis analysis, cytotoxic differences could have easily been overlooked.
DOI der Erstveröffentlichung: 10.1111/acel.13668
URL der Erstveröffentlichung: https://onlinelibrary.wiley.com/doi/10.1111/acel.13668
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-374845
hdl:20.500.11880/33907
http://dx.doi.org/10.22028/D291-37484
ISSN: 1474-9726
1474-9718
Datum des Eintrags: 4-Okt-2022
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Facel.13668&file=acel13668-sup-0001-supinfo.pdf
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Biophysik
M - Physiologie
Professur: M - Prof. Dr. Markus Hoth
M - Prof. Dr. Jens Rettig
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons