A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity
2018 | journal article. A publication with affiliation to the University of Göttingen.
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A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity
Zhou, X.; Friedmann, K. S.; Lyrmann, H.; Zhou, Y.; Schoppmeyer, R.; Knörck, A. & Mang, S. et al. (2018)
The Journal of Physiology, 596(14) pp. 2681-2698. DOI: https://doi.org/10.1113/JP274964
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Details
- Title Variant(s)
- A calcium optimum for CTL and NK cell cytotoxicity
- Authors
- Zhou, Xiao; Friedmann, Kim S.; Lyrmann, Hélène; Zhou, Yan; Schoppmeyer, Rouven; Knörck, Arne; Mang, Sebastian; Hoxha, Cora; Angenendt, Adrian; Backes, Christian S.; Mangerich, Carmen; Zhao, Renping; Cappello, Sabrina ; Schwär, Gertrud; Hässig, Carmen; Neef, Marc; Bufe, Bernd; Zufall, Frank; Kruse, Karsten; Niemeyer, Barbara A.; Lis, Annette; Qu, Bin; Kummerow, Carsten; Schwarz, Eva C.; Hoth, Markus; Zhou, Yangfan
- Abstract
- Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells. We analysed the Ca2+ dependence of CTL and NK cell cytotoxicity and found that in particular CTLs have a very low optimum of [Ca2+ ]i (between 122 and 334 nm) and [Ca2+ ]o (between 23 and 625 μm) for efficient cancer cell elimination, well below blood plasma Ca2+ levels. As predicted from these results, partial down-regulation of the Ca2+ channel Orai1 in CTLs paradoxically increases perforin-dependent cancer cell killing. Lytic granule release at the immune synapse between CTLs and cancer cells has a Ca2+ optimum compatible with this low Ca2+ optimum for efficient cancer cell killing, whereas the Ca2+ optimum for CTL migration is slightly higher and proliferation increases monotonously with increasing [Ca2+ ]o . We propose that a partial inhibition of Ca2+ signals by specific Orai1 blockers at submaximal concentrations could contribute to tumour elimination.
- Issue Date
- 2018
- Journal
- The Journal of Physiology
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Language
- English