HIV modulates the expression of ligands important in triggering natural killer cell cytotoxic responses on infected primary T-cell blasts

Blood. 2007 Aug 15;110(4):1207-14. doi: 10.1182/blood-2006-06-028175. Epub 2007 May 18.

Abstract

The ability of natural killer (NK) cells to kill virus-infected cells depends on the presence of ligands for activation receptors on the target cells. We found the presence of few, if any, NKp30 and NK46 ligands on T cell blasts infected with HIV, although NKp44 ligands were found on infected cells. HIV does induce the NKG2D ligands ULBP-1, -2, and -3. These ligands are involved in triggering NK cells to kill autologous HIV-infected cells, because interfering with the interaction between NKG2D, but not NKp46, on NK cells and its ligands on HIV-infected cells drastically reduced the lysis of infected cells. Interfering with the binding of the NK-cell coreceptors NTB-A and 2B4 to their ligands also decreased destruction by NK cells. The coreceptor ligands, NTB-A and CD48, were also found to be down-regulated during the course of HIV infection. Thus, ligands for NK-cell receptors are modulated during the course of HIV infection, which may greatly alter NK cells' ability to kill the infected cells.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism
  • CD48 Antigen
  • Cytotoxicity, Immunologic / immunology*
  • GPI-Linked Proteins
  • Gene Expression Regulation
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / pathology
  • HIV Seropositivity
  • HIV-1 / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / virology
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • Signaling Lymphocytic Activation Molecule Family
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*

Substances

  • Antigens, CD
  • CD244 protein, human
  • CD48 Antigen
  • CD48 protein, human
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • KLRK1 protein, human
  • Ligands
  • Membrane Glycoproteins
  • Membrane Proteins
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • SLAMF6 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • ULBP1 protein, human
  • ULBP2 protein, human
  • ULBP3 protein, human
  • Signaling Lymphocytic Activation Molecule Family Member 1