NK cells and cytokines in health and disease

NK cells are important lymphocytes characterized by a CD56⁺CD3^- phenotype. Based on the expression of CD56 and CD16, NK cells are divided into CD56^brightCD16^- and CD56^dimCD16⁺ subsets. These two NK cell subsets differ in cytokine secretion and cytoxicity; CD56^brightCD16^- cells are more proficient in cytokine secretion, while CD56^dimCD16⁺ cells are better at mediating cytotoxicity. IL-15 transpresented by dendritic cells plays a critical role in the normal development, homeostasis and activation of NK cells. NK cells secrete several cytokines and chemokines, which play a key role in orchestrating an immune response early aft er exposure to pathogens. The importance of NK cells in clearing viral infections is underscored by the recurrent life-threatening viral infections in patients with absent or dysfunctional NK cells. This has led to studies on NK cells in viral infections such as HIV, cytomegalovirus and hepatitis. Yet, not all NK cell reactions are beneficial. There is some evidence of their overzealous role in a mouse model of diabetes mellitus and other autoimmune diseases. We have been interested in the role of NK cells in immune surveillance against malignant cells to treat cancers that have failed standard therapy. NK cells are thought to contribute to what is called a graft versus leukemia (GvL) effect in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). The goal of this chapter is to provide an overview of NK cell biology and ways in which to exploit this knowledge to treat human disease.