Abstract
Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects. The CD4+ T cell count and plasma level of HIV RNA in the infected individuals were longitudinally followed-up for about 720 days. The proportion of NKG2C+NKG2A− NK cells was higher in subjects from the low set point group and was negatively correlated with the viral load. In addition, strong anti-HIV activities were observed in NKG2C+ NK cells from the HIV-positive donors. Furthermore, a proportion of NKG2C+NKG2A− NK cells >35.45%, and a ratio of NKG2C/NKG2A >1.7 were predictive for higher CD4+ T cell counts 720 days after infection. Collectively, the experimental results allow us to draw the conclusion that NKG2C+ NK cells might exert an antiviral effect and that the proportion of NKG2C+NKG2A− NK cells, and the ratio of NKG2C/NKG2A, are potential biomarkers for predicting HIV disease progression.
Highlights
Natural killer (NK) cells are very important in immune surveillance and contribute to host resistance against viruses and tumors [1,2,3]
We found that in primary HIV-infected patients, the proportion of NKG2C+ NK cells was increased compared with normal controls (NCs) and that the proportion of NKG2C+NKG2A− NK cells was correlated with HIV viral set point
We detected the single expression of NKG2A and NKG2C on NK cells of peripheral blood mononuclear cells (PBMCs) from primary HIV infection (PHI) and age-matched NC subjects
Summary
Natural killer (NK) cells are very important in immune surveillance and contribute to host resistance against viruses and tumors [1,2,3]. Natural killer cells express a large number of inhibitory or activating receptors, such as NKG2 receptors and killer-cell immunoglobulin-like receptors, and bind to their cognate ligands on the surface of target cells [8]. NKG2C or NKG2A forms a heterodimer with C-type lectin CD94, and recognizes the non-classical major histocompatibility complex class I molecule, HLA-E [9]. NKG2C delivers activating signals through immunoreceptor tyrosine-based activation motifs at the cytoplasmic tails of DAP12 transmembrane proteins [10], while NKG2A appears to inhibit NK activation via immunoreceptor tyrosine-based inhibitory motifs in the cytoplasm [11]. Previous studies have shown that the inhibitory receptor NKG2A has a higher affinity for ligands, which is possibly correlated with the presumed dominance of inhibitory signals over activating signals [9, 12, 13]
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