A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1.
OBJECTIVE
Our previous studies have demonstrated that a subclass of soluble human leukocyte antigen-G1 protein (sub-sHLA-G1), that has alpha1 to alpha3 extra-cellular portion but lacks C-terminus of authentic soluble HLA-G1 secreted by trophoblasts, fine-tunes the release of cytokines from peripheral blood mononuclear cells (PBMCs) chiefly by counterbalancing membrane-bound HLA-G1 (mHLA-G1), and thereby may play a role in maintaining pregnancy. In this study, we investigated whether the presence of sHLA-G1 protein altered the release of cytokines from decidual mononuclear cells (DMCs) which are localized at the interface of feto-maternal interaction and whose cell population is completely different from PBMCs.


METHODS
We cultured peripheral DMCs with either HLA-A and -B lacking B lymphoblast cell line (721.221 cells) or the cells transfected with mHLA-G1 (721.221-G1 cells) with or without sub-sHLA-G1. Cytokines concentrations in the culture media were determined by an enzyme-linked immunosorbent assay.


RESULTS
Regardless of the presence of mHLA-G1 expressing cells, the addition of the recombinant sub-sHLA-G1 protein in the DMC culture media decreased the amounts of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, with the release of IL-4 from DMCs being unchanged.


CONCLUSIONS
The sub-sHLA-G1 protein modulates the release of cytokines from DMCs additively to mHLA-G1 expressing cells. In view of the distinct fetomaternal interaction during implantation, it appears that sHLA-G1 might play a role in the establishment of pregnancy by regulating cytokine release in concert with mHLA-G1.
Kanai
Takao
T
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655 Tokyo, Japan.
Fujii
Tomoyuki
T
Kozuma
Shiro
S
Miki
Akinori
A
Yamashita
Takahiro
T
Hyodo
Hironobu
H
Unno
Nobuya
N
Yoshida
Shiro
S
Taketani
Yuji
Y
D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis*; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003470:Culture Media; D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma