Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E.
During normal early pregnancy, a particular immune environment in the decidua and the expression of non-classical HLA-G and HLA-E molecules on the invading trophoblast are assumed to be essential for the tolerance of the fetus. To assess whether HLA-G and HLA-E influence the cytokine production of their putative target cells [large granular lymphocytes (LGL)], we analysed the concentrations of tumour necrosis factor (TNF-alpha), interferon (IFN)-gamma, interleukin (IL)-10, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) in supernatants of isolated first trimester LGL co-cultured with HLA-G or HLA-E transfected K-562 leukaemia cells lacking the classical HLA class I and II molecules. In comparison with that observed with untransfected K-562 cells, co-culture of LGL with HLA-G-expressing cells significantly reduced the concentration of all cytokines investigated (TNF-alpha, IL-10 and GM-CSF, P < 0.01; IFN-gamma and IL-13, P < 0.05). In contrast, co-culture of LGL with HLA-E-expressing cells significantly (P < 0.01) decreased only IL-10 production, although a strong tendency towards reduced IL-13 levels was also observed. In the co-culture system presented, membrane-bound HLA-G and, to a lesser extent, HLA-E expression affected cytokine release by decidual LGL in a manner not consistent with the Th1/Th2 paradigm. In conclusion, our data are indicative of a general immune-suppressive effect of HLA-G on LGL activity.
Rieger
L
L
Department of Obstetrics and Gynaecology, Julius-Maximilians-University, Wuerzburg, Germany.
Hofmeister
V
V
Probe
C
C
Dietl
J
J
Weiss
E H
EH
Steck
T
T
Kämmerer
U
U
D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis*; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D020014:K562 Cells; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097625:HLA-E Antigens
D003470:Culture Media; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D016753:Interleukin-10; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D000097625:HLA-E Antigens