Soluble HLA-G molecules induce apoptosis in natural killer cells

Am J Reprod Immunol. 2006 Jul;56(1):68-76. doi: 10.1111/j.1600-0897.2006.00395.x.

Abstract

Membrane-bound human leukocyte antigen-G (HLA-G) molecules are primarily expressed by cytotrophoblasts of the fetus. They are thought to protect the fetus from immunologic attack by the maternal immune system and have recently been associated with transplantation graft acceptance. In addition, soluble HLA-G molecules (sHLA-G) have been shown to play a role in the success of pregnancies, but are upregulated in certain cancers. However, the exact mechanism for this regulation has remained elusive. The aim of this study was to examine the mechanism by which sHLA-G interact with natural killer (NK) cells in vitro. sHLA-G effectively blocked NK lysis of target cells via fracticide killing of NK cells by apoptosis. These studies support the protective role of sHLA-G in immunologic reactions by interacting with NK cells, thus providing a regulatory function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies / pharmacology
  • Antigens, CD / immunology
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic / drug effects
  • Dose-Response Relationship, Drug
  • HLA Antigens / biosynthesis
  • HLA Antigens / genetics
  • HLA Antigens / pharmacology*
  • HLA-B7 Antigen / pharmacology
  • HLA-G Antigens
  • HeLa Cells
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / pharmacology*
  • Humans
  • In Situ Nick-End Labeling
  • K562 Cells
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / immunology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology

Substances

  • Antibodies
  • Antigens, CD
  • HLA Antigens
  • HLA-B7 Antigen
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Immunologic
  • Recombinant Proteins