Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Aug 5;221(8):e20231222.
doi: 10.1084/jem.20231222. Epub 2024 Jun 6.

Five decades of natural killer cell discovery

Lewis L Lanier  1   2
Affiliations
Review

Five decades of natural killer cell discovery

Lewis L Lanier. J Exp Med. .

Abstract

The first descriptions of "non-specific" killing of tumor cells by lymphocytes were reported in 1973, and subsequently, the mediators of the activity were named "natural killer" (NK) cells by Rolf Kiessling and colleagues at the Karolinska Institute in 1975. The activity was detected in mice, rats, and humans that had no prior exposure to the tumors, major histocompatibility complex (MHC) antigen matching of the effectors and tumor cells was not required, and the cells responsible were distinct from MHC-restricted, antigen-specific T cells. In the ensuing five decades, research by many labs has extended knowledge of NK cells beyond an in vitro curiosity to demonstrate their in vivo relevance in host defense against tumors and microbial pathogens and their role in regulation of the immune system. This brief Perspective highlights a timeline of a few selected advancements in NK cell biology from a personal perspective of being involved in this quest.

PubMed Disclaimer

Conflict of interest statement

Disclosures: L.L. Lanier advises Cullinan Oncology, Dragonfly, DrenBio, Edity, GV20, IMIDomics, InnDura Therapeutics, Innovent, Nkarta, oNKo, Obsidian Therapeutics, SBI Biotech, and Stamford Pharmaceuticals to advance NK cell–based therapies.

Figures

Figure 1.
Figure 1.
NK cell discovery timeline. Selected milestones in five decades of NK cell discovery. CAR, chimeric antigen receptor.
See this image and copyright information in PMC

References

    1. Aguilar, O.A., Berry R., Rahim M.M.A., Reichel J.J., Popović B., Tanaka M., Fu Z., Balaji G.R., Lau T.N.H., Tu M.M., et al. . 2017. A viral immunoevasin controls innate immunity by targeting the prototypical natural killer cell receptor family. Cell. 169:58–71.e14. 10.1016/j.cell.2017.03.002 - DOI - PubMed
    1. Anderson, P., Caligiuri M., Ritz J., and Schlossman S.F.. 1989. CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex. Nature. 341:159–162. 10.1038/341159a0 - DOI - PubMed
    1. Arase, H., Mocarski E.S., Campbell A.E., Hill A.B., and Lanier L.L.. 2002. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science. 296:1323–1326. 10.1126/science.1070884 - DOI - PubMed
    1. Bauer, S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., and Spies T.. 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 285:727–729. 10.1126/science.285.5428.727 - DOI - PubMed
    1. Biron, C.A., Byron K.S., and Sullivan J.L.. 1989. Severe herpesvirus infections in an adolescent without natural killer cells. N. Engl. J. Med. 320:1731–1735. 10.1056/NEJM198906293202605 - DOI - PubMed