[Expression of the molecules HLA-G and HLA-E modulates cytokine production of monocyte generated dendritic cells].
OBJECTIVE
Preferential secretion of Th1-like cytokine is mainly a property of monocyte derived dendritic cells (DC). Since normal early pregnancy is characterized by a shift towards a Th2-like cytokine pattern, it may be assumed that cytokine secretion by DC during early pregnancy could be modulated by the non-classical HLA molecules G and E present on invasive trophoblast.


METHODS
DC were cultivated from monocytes isolated from peripheral blood mononuclear cells. DC were cocultured with K-562 leukemia cells lacking the class I and II HLA antigens transfected with either HLA-G or HLA-E or ultratransfected cells (controls) and the concentrations of IL-8, IL-10, IL-12p70, IL-18 and TNF-alpha were measured in the supernatants by ELISA.


RESULTS
Coculture with ultratransfected cells resulted in a significant increase of the production of IL-8 and TNF-alpha by mature and immature DC and of IL-10 by immature DC (p < 0.01). When cocultured with HLA-G and HLA-E transfected K-562 cells, the secretion of IL-8 by immature and mature DC and that of IL-10 and TNF-alpha by immature DC was significantly (p < 0.01) decreased. The contact with HLA-G and HLA-E transfected cells had no effect on the production of IL-12p70 and IL-18 by DC.


CONCLUSIONS
These results show that DC react with an increased cytokine release upon contact with cells lacking HLA class I and II antigens. The suppressive effect of HLA-G and HLA-E on the secretion of TNF-alpha (Th1 cytokine), IL-10 (Th2 cytokine) and IL-8 (chemokine) by immature DC could be interpreted as further evidence for the central immunotolerance role of HLA-G and HLA-E during early pregnancy.
Steck
T
T
Frauenklinik und Poliklinik der Universität Würzburg, Germany. thomas.steck@mail.uni-wuerzburg.de
Rieger
L
L
Rödel
E
E
Dietl
J
J
Kämmerer
U
U
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014162:Transfection; D000097625:HLA-E Antigens
D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D000097625:HLA-E Antigens