Chapter Fifteen - NK cells and chemokines

Abstract

Natural killer (NK) cells belong to a distinct lineage of lymphocytes that play an important role in the early phase of immune responses against certain microbial pathogens by exhibiting cytotoxic functions and secreting a number of cytokines and chemokines. NK cells develop from a common lymphoid precursor resident in the bone marrow (BM) that is considered the main site of their generation. The BM microenvironment provides a rich source of cytokines and growth factors and allows intimate contact between developing NK cells and stromal cells, which is required for their full maturation. Individual NK cell subsets displaying unique functional features, and tissue locations have been identified both in mouse and humans. Involvement of chemokines in the regulation of DC-mediated NK cell priming and effector functions has also been documented and should be taken into account when analyzing the role of chemokines in NK cell-dependent immune responses. Studies in man and mouse have shown that NK cells are distributed in several organs under normal conditions. Their frequency is comparatively high in nonlymphoid organs such as the lung, the liver and the mucosal tissue of maternal uterus, and rare in thymus and lymph nodes. Chemotactic factors, including chemokines, play critical roles in the regulation of NK cell migration across endothelium and into the tissues. The differences in chemokine receptor expression together with distinct adhesive properties of different NK cell subsets as well as activated NK cells, imply that they have multiple routes of circulation and trafficking patterns. Besides their role in the regulation of NK cell trafficking, chemotactic molecules can also affect NK cell effector functions by regulating their priming and their ability to kill and secrete cytokines.