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

Abstract

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.

Identification of a Novel Neutrophil Population: Proangiogenic Granulocytes in Second-Trimester Human Decidua

“…Thus, some disease states may mimic the physiological inflammation associated with pregnancy. Numerous cytokines and chemokines, including GM-CSF, IFN-g, and TNF-a, are produced by the decidua (53,54). In tumors, these cytokines and growth factors are known to upregulate neutrophil expression of CD191 and CD195, and to prime neutrophil migration toward CC chemokines, such as CCL2-5 (55-57).…”

No evidence for apoptosis of decidual leucocytes in normal and molar pregnancy: implications for immune privilege

“…Decidual T cells can produce cytokines including interleukin (IL)-3, IL-4, transforming growth factor (TGF)-b 1 , TNF-a and interferon (IFN)-g [42][43][44][45] and it has been suggested that deficient production by decidual T cells of cytokines, such as IL-4 and LIF, may lead to pregnancy failure [47]. Recently, the non-classical class I HLA-G and HLA-E molecules, both of which are expressed by fetal trophoblast cells, have been reported to suppress production by isolated first-trimester uterine NK cells of cytokines including IL-10, IL-13, TNF-a, granulocyte macrophage colony-stimulating factor (GM-CSF) and IFN-g [49]. Whether HLA-G and HLA-E regulate the production of cytokines by decidual T cells and macrophages is unknown.…”

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

“…proposed to be involved in the modulation of maternal immune responses and has for instance been shown to inhibit cytokine production and reduce NK cell cytotoxicity, to eliminate activated cytotoxic CD8 + T cells and to induce production of TGF-β by APCs (Rieger et al, 2002;Hunt et al, 2005). Although less pronounced, HLA-E has also been shown to inhibit NK cell cytotoxicity (King et al, 2000a).…”