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.
LaBonte
Michelle L
ML
Department of Biological Sciences, Bridgewater State College, Bridgewater, USA.
McKay
Paul F
PF
Letvin
Norman L
NL
D000818:Animals; D003175:Complement C2 / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008253:Macaca mulatta; D055654:NK Cell Lectin-Like Receptor Subfamily C; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055607:Receptors, Natural Killer Cell; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus
D003175:Complement C2; D016207:Cytokines; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell