Increased frequency of human leukocyte antigen-E inhibitory receptor CD94/NKG2A-expressing peritoneal natural killer cells in patients with endometriosis

Fertil Steril. 2008 May;89(5 Suppl):1490-6. doi: 10.1016/j.fertnstert.2007.05.018. Epub 2007 Aug 13.

Abstract

Objective: To analyze the frequency of peritoneal natural killer (NK) cells expressing the human leukocyte antigen (HLA)-E receptor CD94/NKG2A in patients with endometriosis.

Design: Case-control study.

Setting: University hospital.

Patient(s): Stage III and stage IV endometriosis, according to the revised American Society for Reproductive Medicine classification, was laparoscopically and histologically confirmed in 11 and 9 patients, respectively; 13 subjects without endometriosis were selected for the control group.

Intervention(s): Collection of peripheral venous blood, peritoneal fluid, endometriotic tissue, and normal endometrium in subjects undergoing laparoscopy.

Main outcome measure(s): Surface expression levels of CD94/NKG2A and CD94/NKG2C were detected by three-color cytofluorometric analysis. Semiquantitative HLA-E messenger RNA expression analysis was performed in endometriotic lesions and in eutopic endometrium. NK cell-mediated cytotoxic activity toward HLA-E positive target, DT360 cell line, was also determined.

Result(s): In women with endometriosis, the percentage of CD94/NKG2A-positive peritoneal NK cells was significantly higher than in the control group. The CD94/NKG2A ligand, HLA-E, was detected at high levels in endometriotic tissue as messenger RNA transcript. Target cells bearing HLA-E were resistant to NK cell-mediated lysis in a CD94/NKG2A-dependent manner.

Conclusion(s): Increased expression of CD94/NKG2A in peritoneal NK cells may mediate the resistance of endometriotic tissue to NK cell-mediated lysis, thus contributing to the progression of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ascitic Fluid / immunology*
  • Ascitic Fluid / metabolism
  • Ascitic Fluid / pathology
  • Case-Control Studies
  • Disease Progression
  • Endometriosis / blood
  • Endometriosis / immunology*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immune Tolerance / immunology
  • Immunity, Cellular / immunology
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology*
  • Lymphocyte Count
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D / blood
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Immunologic / blood
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I
  • KLRC1 protein, human
  • KLRC2 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell