Natural killer cell

Lore & Background

The discovery that a unique type of lymphocyte was responsible for 'natural' or spontaneous cytotoxicity was made in the early 1970s by doctoral student Rolf Kiessling and postdoctoral fellow Hugh Pross, in the mouse, and by Hugh Pross and doctoral student Mikael Jondal in the human. The mouse and human work was carried out under the supervision of professors Eva Klein and Hans Wigzell, respectively, of the Karolinska Institute, Stockholm. Using discontinuous density centrifugation, and later monoclonal antibodies, natural killing ability was mapped to the subset of large, granular lymphocytes known today as NK cells.

Reader's Guide

Natural killer cells are significant as a critical component of the innate immune system, providing rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens. Their ability to recognize and kill cells lacking MHC class I molecules fills a gap in immune surveillance, as such cells cannot be detected by T lymphocytes. The discovery of NK cells in the early 1970s resolved long-standing observations of 'natural' cytotoxicity that had been dismissed as artifacts. Their role extends beyond innate immunity, as they also contribute to adaptive immune responses by formulating antigen-specific immunological memory. This dual role has made NK cell activity increasingly important in research for potential cancer therapy and HIV therapy. The identification of subtypes—CD56bright (cytokine-producing, immunoregulatory) and CD56dim (cytotoxic, CD16-positive)—has refined understanding of their diverse functions. NK cell activation is determined by the balance of inhibitory and activating receptor stimulation, a principle that underpins their self-tolerance and effector functions. Their legacy includes the development of the K562 51chromium-release assay, a standard method for detecting human NK functional activity, enabling global comparison of experimental data.

Did You Know?

• NK cells represent 5–20% of all circulating lymphocytes in humans.
• NK cells can be identified by the presence of CD56 and the absence of CD3 (CD56+, CD3−).
• The K562 51chromium-release assay is the most commonly used assay to detect human NK functional activity.