Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E

• Published in: Molecular human reproduction 2002-03, Vol.8 (3), p.255-261
• Main Authors: Rieger, L., Hofmeister, V., Probe, C., Dietl, J., Weiss, E.H., Steck, T., Kämmerer, U.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cells, Cultured; Culture Media; cytokine; Cytokines - biosynthesis; Decidua - cytology; Decidua - immunology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; HLA Antigens - genetics; HLA Antigens - immunology; HLA-E; HLA-E Antigens; HLA-G; HLA-G Antigens; Humans; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-13 - biosynthesis; K-562; K562 Cells; LGL; Lymphocytes - cytology; Lymphocytes - immunology; Mother. Fetoplacental unit. Mammary gland. Milk; Pregnancy; Pregnancy Trimester, First; Pregnancy. Parturition. Lactation; Th1 Cells - immunology; Th2 Cells - immunology; Transfection; Tumor Necrosis Factor-alpha - biosynthesis; Vertebrates: reproduction
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/8.3.255

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-α), interferon (IFN)-γ, 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-α, IL-10 and GM-CSF, P < 0.01; IFN-γ 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.