Abstract
Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.
Highlights
Natural killer (NK) cells are large granular lymphocytes and the first line of defense against tumors and viral infection [1–3]
Previous studies reported that Matrix Metalloproteinases (MMPs) levels are increased in human immunodeficiency virus (HIV)-infected CD4 T cells and that MMPs induce the release of NKG2DL into the peripheral circulation, resulting in decreased expression of NK Group 2D (NKG2D) on NK cells and a decrease in the killing ability of NK cells [73, 74]
Jiang et al reported that the proportion of transforming growth factor (TGF)-bpos or IL-10pos NK cells is increased in HIV infection; in vitro experiments indicated that recombinant IL-10 and TGF-b suppress NK cell function [13]
Summary
Natural killer (NK) cells are large granular lymphocytes and the first line of defense against tumors and viral infection [1–3]. NK cells can initiate immune responses to target tumors and virus-infected cells by releasing perforin, Granzyme B, cytokines, and via Fas/Fas-L pathway [3, 6]. Research indicates that NK cells play a crucial role in anti-HIV immune responses [11] but fail to control HIV infection due to dysfunction or exertion of negative regulatory effects [12, 13]. NK cells are considered potentially important in the treatment of HIV infection and have even been applied to the elimination of viral reservoirs that. This review focuses on the characteristics of NK cells during HIV infection and summarizes the prospects of immunotherapies based on NK cells as means of eliminating viral reservoirs
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