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.