Evidence of NK cell dysfunction in SIV-infected rhesus monkeys: Impairment of cytokine secretion and NKG2C/C2 expression

Defects in the adaptive immune response have been extensively characterized in human immunodeficiency virus type-1 (HIV-1)-infected individuals; however, much less is known about the function of natural killer (NK) cells during the course of HIV-1 infection. In the present study, we demonstrate that the NK cells from simian immunodeficiency virus (SIV)-infected rhesus monkeys are significantly impaired in their ability to secrete IFN-gamma, TNF-alpha, and IL-2, while NK cell function in SIV-infected long-term non-progressor monkeys is similar to that of normal monkeys. These findings suggest that abnormal NK cell activity may contribute to the global immune dysfunction observed in HIV-1-infected individuals. NK cell function is modulated by several families of cell surface receptors, including the CD94/NKG2 family. We evaluated the messenger RNA levels of these inhibitory and activating NKG2 molecules in SIV-infected rhesus monkeys. These experiments demonstrate that the activating molecules NKG2C and NKG2C2 are significantly down-regulated in peripheral blood mononuclear cells of SIV-infected rhesus monkeys, suggesting that the dysregulation of these molecules may contribute to the abnormal NK cell function observed in the setting of infection.