Chemokine biology of NK cells and γδ T cells

Abstract

Natural killer (NK) cells and γδ T cells are populations of lymphocytes that mediate immunity against pathogens and malignant tumors. Both generally exhibit significant cytotoxicity, produce high levels of inflammatory cytokines and chemokines, and share the expression of cellular receptors (generally designated NK receptors) for the detection of MHC class I and class Ib proteins and other cell surface proteins. NK cells are large granular lymphocytes that play important roles in host defense against viral, bacterial, and parasitic infections as well as in the surveillance for malignant cells. In addition to their cytotoxic capabilities, NK cells serve as regulators of immune responses through the release of a variety of cytokines and chemokines. NK cells are bone marrow-derived lymphocytes that were originally characterized by their ability to spontaneously mediate lysis of certain tumor cell lines, their large granular morphology, and their lack of a T cell receptor and CD3 complex. NK cells do not use the specialized gene rearrangement machinery that assembles T and B cell antigen receptors. Instead, NK cells express both inhibitory and activating cell surface receptors. Inhibitory receptors include C-type lectin family receptors, such as Ly49 and CD94/NKG2, or Ig superfamily receptors such as killer immunoglobulin-like receptors (KIR). These receptors generally recognize MHC class I (class Ia) and class Ib (HLA-E in human and Qa-1 in mice) proteins. A number of activating receptors on NK cells have been described that are alternative forms of Ly49, KIR family (termed KAR), and CD94/NKG2 receptors and that have similar specificities as their inhibitory forms. In addition, unique activating receptors are also expressed such as the NKG2D receptor that recognizes MICA/B, Rae1, and H60, CD16 that binds to IgG, NKp44/NKp46 that recognize viral hemagglutinins, and NKp30 whose ligands are not well characterized. The primary peripheral NK cells present in humans and mice are mature cells with decreasing frequencies in blood, spleen, and bone marrow, respectively. Human NK cells comprise 15% of all circulating lymphocytes and can be divided into two subsets, CD56bright and CD56dim, each subset having unique functional attributes and distinct roles in the human immune response [1].