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Abstract

Natural killer (NK) cells are major effectors of the innate immune response and purported to play an influential role in the spontaneous control of HIV infection. In the present study, we compared the phenotypes of NK cells in the peripheral blood of three groups of subjects with chronic HIV-1 infection, HIV controllers, and healthy donors.The results showed that while the dysfunctional NK cell subset (CD56-/CD16+) expanded in both chronic patients and controllers, they decreased in chronic patients regardless of their superior ability to produce cytokines and remained unchanged in controllers. In addition, we found thatpersons living with chronic HIV-1 had suppressed NKp80, NKp46, and NKG2D expressions on NK cells compared to healthy donors.In contrast, NKG2D expression was substantially higher in controllers than in chronic patients (M=97.67, p<0.001). There were no significant differences in inhibitory receptors KIR3DL1 and KIR2DL1 expressions. Plasma cytokine IFN-γ, TNF-αand IL-12, which can enhance the cytotoxicity of NK cells, showed higher levels in HIVcontrollers.Overall, our study revealed a previously underappreciated link between NK cell phenotype and the control of HIV replication. Collectively, the evidence points to an essential role for the expressions of NKp80, NKp46, and especially NKG2D on NK cells in limiting viral spread, eliminating infected cells, and slowing the progression from HIV-1 infection to AIDS.