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

Eur J Immunol. 2006 Sep;36(9):2424-33. doi: 10.1002/eji.200635901.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Complement C2 / biosynthesis*
  • Cytokines / metabolism*
  • Flow Cytometry
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / virology*
  • Macaca mulatta
  • NK Cell Lectin-Like Receptor Subfamily C
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Natural Killer Cell
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus


  • Complement C2
  • Cytokines
  • KLRC1 protein, human
  • KLRC2 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell