posted on 2021-02-19, 20:43authored byJeehun Park, Yerin Shin, Jung Min Kim, SoonHo Kweon, Ah Young Song, Yujin Baek, Jinho Kim, Duck Cho, Hun Sik Kim, Junsang Doh
Natural
killer (NK) cells are a subset of innate lymphoid cells
playing an important role in immune surveillance and early defense
against infection and cancer. They recognize and directly kill infected
or transformed cells. At the same time, they produce various cytokines
and chemokines to regulate other immune cells. NK cell activity can
be a useful marker for health screenings because impaired NK cell
functions may indicate a more susceptible environment for infection
or tumor development. Currently, most NK cell activity assays are
focused on measuring either cytokine secretion, in particular, interferon
γ (IFN-γ), or cytotoxicity against target cells such as
K562, thus only providing partial information on NK cell activity.
In order to develop a comprehensive test for measuring NK cell function,
cytotoxicity and cytokine secretion ability should be measured simultaneously.
In addition, current NK cell assays are performed by stimulating NK
cells with cocktails of cytokines, antibody-coated beads, or live
target cells. In this study, we developed multifunctional microparticles
for NK cell activity assay (MNAs) that allow simultaneous stimulation
and sensing various NK cell activities, including cytokine secretion
and cytotoxicity. The surfaces of MNAs are decorated with multiple
functional biomolecules, including antibodies that stimulate NK cells
by engaging NK cell activating receptors, antibodies that can capture
cytokines secreted by NK cells, and a peptide sensor that reacts with
granzyme B, a key molecule released by NK cells for cytotoxicity.
The performances of MNAs are assessed using flow cytometry and live
cell imaging. NK cell activity is measured by simply mixing MNAs with
NK cells and performing flow cytometry, and the results are comparable
to those measured by standard NK cell activity assays.