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Published on: February 22, 2020
Target-induced natural killer cell loss as a measure of NK cell responses
1Cancer Immunology Research Unit, The Canberra Hospital, Australian Capital Territory, Australia. Hilary.Warren@anu.edu.au
Abstract:
The interaction of natural killer cells with susceptible target cells triggers NK cell activation, eliciting not only NK cell cytotoxicity and cytokine secretion, but also NK cell death. This study shows that following target cell interaction there is a substantial loss of NK cells, the extent of which correlates with measures of NK cell cytotoxicity assessed by the target cell release of (51)Cr and by the externalisation of the lysosomal marker LAMP-1 (CD107a) which is assessed on the remaining NK cells. This is the case for the killing of K562 (natural killing) and the CD20 mAb (Rituximab)-mediated killing of RAJI cells and autologous B cells (antibody-dependent cell cytotoxicity). This target-induced NK loss (TINKL) provides a sensitive and specific measure of NK cell responses appropriate to a clinical laboratory setting.
Insights
Natural killer (NK) cells undergo significant cell death after interacting with target cells. This target-induced NK loss (TINKL) correlates with NK cell cytotoxicity and offers a new clinical measure.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial immune cells involved in cytotoxicity and cytokine secretion.
- NK cell activation by target cells can paradoxically lead to NK cell death.
Purpose of the Study:
- To investigate and quantify NK cell death following target cell interaction.
- To establish target-induced NK loss (TINKL) as a measurable indicator of NK cell function.
Main Methods:
- Assessed NK cell loss after co-culture with target cells (K562, RAJI, autologous B cells).
- Measured NK cell cytotoxicity using chromium-51 ((51)Cr) release assay.
- Quantified LAMP-1 (CD107a) externalization on remaining NK cells as a marker of activation and degranulation.
Main Results:
- A substantial loss of NK cells was observed post-interaction with target cells.
- The extent of NK cell loss correlated directly with NK cell cytotoxicity.
- This correlation held true for both natural and antibody-dependent cell-mediated cytotoxicity.
Conclusions:
- Target-induced NK loss (TINKL) is a significant phenomenon following NK cell activation.
- TINKL serves as a sensitive and specific biomarker for NK cell responses.
- TINKL is suitable for assessment in clinical laboratory settings.
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