Re-educating natural killer cells

Abstract

The development and function of natural killer (NK) cells is dictated by signals received through activating and inhibitory receptors expressed on the cell surface. During their maturation in the bone marrow, NK cells undergo an education process that ensures they are tolerant to healthy peripheral tissues. Several recent studies advance our understanding of self-tolerance mechanisms at work in NK cells. These studies demonstrate that the developmental programming in NK cells is not fixed, and that perturbations to the peripheral environment (via transplantation or viral infection, for example) greatly influence the ability of mature NK cells to mount an effector response. This newfound ability of mature NK cells to be "re-educated" may be clinically applicable in the immunotherapeutic use of NK cells against infection and cancer.

Figure 1.

Education and re-education of NK cells. The figure depicts the “education” of developing NK cells in different bone marrow environments (left) and the experimental “re-education” of mature NK cells in different peripheral environments (right). (A) Immature NK cells expressing inhibitory receptors that engage MHC class I become responsive mature effector cells. (B) Immature NK cells expressing inhibitory receptors that do not engage MHC class I become anergic cells. (C) Immature NK cells lacking inhibitory receptors that can engage MHC class I also become anergic cells. (D) Mature responsive NK cells that are adoptively transferred into a MHC class I–deficient environment become anergic. (E) Mature anergic NK cells (expressing inhibitory receptors for MHC class I) that are adoptively transferred into a MHC class I–sufficient setting become responsive. (F) During viral infection and inflammation, mature anergic NK cells (lacking inhibitory receptors for MHC class I) become activated and hyperresponsive effector cells.