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


METHODS
Case-control study.


METHODS
University hospital.


METHODS
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.


METHODS
Collection of peripheral venous blood, peritoneal fluid, endometriotic tissue, and normal endometrium in subjects undergoing laparoscopy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Galandrini
Ricciarda
R
Department of Experimental Medicine, University "La Sapienza," Rome, Italy. ricciarda.galandrini@uniroma1.it
Porpora
Maria Grazia
MG
Stoppacciaro
Antonella
A
Micucci
Federica
F
Capuano
Cristina
C
Tassi
Ilaria
I
Di Felice
Alessia
A
Benedetti-Panici
Pierluigi
P
Santoni
Angela
A
D000328:Adult; D001202:Ascitic Fluid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D004715:Endometriosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D018655:Lymphocyte Count; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000097:blood / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human