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Received Oct 6, 2017; Accepted Dec 19, 2017
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1. Introduction
Natural killer (NK) cells are lymphoid cells of the innate immune system included in the recent redefined family of innate lymphoid cells (ILC) as type 1 ILC [1, 2] and represent about 10–20% of total lymphocytes in human peripheral blood (PB) [3]. The new ILC classification reconsiders the innate cells and their specialized functions based on transcription factor and cytokine expression, underlying some similarities with T cell functions [2]. NK cells have both effector and regulatory activities against tumor and virus-infected cells through cytotoxicity and cytokine release. They are characterized by cytoplasmic granules and exert their cytotoxicity by releasing perforin and granzyme molecules, able to trigger target cell death by apoptosis. NK cells also play a crucial role in the production of immunoregulatory cytokines and chemokines [3–8]. These soluble factors impact on recruitment and function of other hematopoietic cells, placing NK cells as orchestrators in the crosstalk between innate and adaptive immunity [9, 10]. NK cells are characterized by a wide array of activating and inhibitory receptors that are finely tuned according to their functions and the hosting microenvironment [2].
Based on the expression density of the CD56 and CD16 surface antigens, two predominant morphologically and functionally different NK cell subsets have been identified in peripheral blood (PB-NK) [8, 11]. Approximately 95% of PB-NK cells are characterized by a CD56dimCD16+ phenotype, can release cytolytic granules containing perforin and granzyme, and exert cytotoxicity [12]. The other subpopulation in PB-NK (about 5%) shows a CD56brightCD16− phenotype: these cells are poorly cytotoxic, yet they are able to secrete high levels of cytokines [8, 11]. CD56brightCD16− NK cells are mostly present in secondary lymphoid organs, and recent studies have attributed a new immunomodulatory role in the context of chronic inflammatory conditions (autoimmune disease), the ability to inhibit proliferation of autologous CD4+ T cells [13, 14].
The CD56brightCD16− NK cell subset has been supposed to represent preterminally differentiated NK cells, capable of cell proliferation and cytokine...