Kopcow HD, Rosetti F, Leung Y et al.T cell apoptosis at the maternal-fetal interface in early human pregnancy, involvement of galectin-1. Proc Natl Acad Sci USA 105:18472-18477

Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2008; 105(47):18472-7. DOI: 10.1073/pnas.0809233105
Source: PubMed


The human fetus is not rejected by the maternal immune system despite expressing paternal antigens. Natural killer cells, the major lymphocyte population of the human decidua (dNKs), express genes with immunomodulatory potential. These include galectin-1 (gal1), a lectin with apoptotic activity on activated CD8(+) T cells, Th1 and Th17 CD4(+) cells. Although many cell types at the maternal-fetal interface also produce gal1, its production by dNKs has been used here to study its function in pregnancy. Media conditioned by dNKs containing gal1 induced apoptosis of activated T cells. This effect was blocked by anti-gal1 antibodies. Decidual T (dT) cells but not peripheral T (pT) cells bound gal1 and presented a distinct glycophenotype compatible with sensitivity to gal1. Annexin V staining, TUNEL, and hypodiploidy showed a substantial proportion of apoptotic dT cells. Immunohistochemistry revealed widespread expression of gal1 as well as periglandular apoptotic dT foci that colocalized with dNKs. Thus, secretion of gal1 by dNKs and other decidual cells contributes to the generation of an immune-privileged environment at the maternal-fetal interface.

Download full-text


Available from: Hernan D Kopcow, Oct 02, 2014
1 Follower
38 Reads
  • Source
    • "Galectin-1 signalling at the maternal– fetal interface gal-1 exerts multiple biological functions including cell differentiation, proliferation, growth, apoptosis, migration, adhesion, transformation, cell– cell and cell–matrix interactions and even pre-mRNA splicing (Camby et al., 2006, Nakahara and Raz, 2006). These functions influenced by gal-1 play important roles in the orchestration of developmental processes at the feto-maternal interface, such as the transformation of endometrial cells during decidualization, the apoptosis of activated T cells to mediate maternal tolerance and the differentiation of trophoblasts into distinct phenotypes with different invasive and functional properties (von Wolff et al., 2005; Kopcow et al., 2008; Kolundzic et al., 2011; Tirado-Gonzalez et al., 2013). However, the study and identification of receptors for gal-1 is only emerging and many possible interactions for the modulation of cellular functions remain to be elucidated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND After recognition of its pivotal contribution to fetomaternal tolerance, the study of galectin-1 (gal-1) functions in the context of pregnancy became an attractive topic in reproductive medicine. Despite considerable advances in the understanding of the immuno- and growth-regulatory properties of gal-1 at the fetal-maternal interface, many functional aspects of this lectin in reproduction are only emerging.METHODS The published literature was searched using Pubmed focusing on gal-1 signalling and functional properties at the maternal-fetal interface, including data on its implication in pregnancy disorders and malignancies of the female reproductive system. Papers discussing animal and human studies were included.RESULTSThis review provides an overview of gal-1 functions during pregnancy, such as modulation of maternal immune responses and roles in embryo implantation and placentation. We also emphasize the role of gal-1 in key regulatory processes, including trophoblast migration, invasion, syncytium formation and expression of non-classical MHC class I molecules (HLA-G). In addition, we argue in favour of gal-1 pro-angiogenic properties, as observed in tumourigenesis and other pathological settings, and its implication in the angiogenesis process associated with early gestation.CONCLUSION The involvement of gal-1 in the regulation of different processes during the establishment, development and maintenance of pregnancy could be described as unique. Gal-1 has emerged as an important lectin with major functions in pregnancy.
    Human Reproduction Update 09/2013; 20(2). DOI:10.1093/humupd/dmt040 · 10.17 Impact Factor
  • Source
    • "It exerts major roles in the immune system (Perillo et al., 1995; Rubinstein et al., 2004) and is involved in the immune-mediated fetal tolerance during pregnancy, promoting the generation of tolerogenic dendritic cells (DCs), inducing IL-10 expressing T regulatory cells and a Th2 cytokine shift by provoking apoptosis of susceptible Th1 cells (Blois et al., 2007; Kopcow et al., 2008). Gal-1 displays intracellular (i.e. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.
    Molecular Human Reproduction 01/2013; 19(1):43-53. DOI:10.1093/molehr/gas043 · 3.75 Impact Factor
  • Source
    • "Apoptosis of activated T cells Apoptosis of activated T cells Mishan-Eisenberg et al. (2004) Th1–Th2 switch Th1–Th2 switch Liu (2005); Toscano et al. (2007) Essential for pregnancy Yes Yes Seppala et al. (2002) Liu et al. (2006) Blois et al. (2007) Kopcow et al. (2008) Carbohydrate recognition Galactose Galactose Barondes et al. (1994) Ca 2+ independent Ca 2+ independent Walzel et al. (2006) N-glycans a N-and O-glycans (However, N-glycan recognition essential for T cell apoptosis and Th1-Th2 switch) Known common receptors CD45 CD45 Rachmilewitz et al. (2003) Elola et al. (2005) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Glycodelin A (GdA) is one of the progesterone inducible endometrial factors that protect the fetal semi-allograft from maternal immune rejection. The immunoregulatory effects of GdA are varied, with diverse effects on the fate and function of most immune cell types. Its effects on T cells are particularly relevant as it is capable of regulating T cell activation, differentiation, as well as apoptosis. We have previously reported that GdA triggers mitochondrial stress and apoptosis in activated T cells by a mechanism that is distinct and independent of its effects on T cell activation. In this study we describe the characterization of a cell surface receptor for GdA on T cells. Our results reveal a novel calcium-independent galactose-binding lectin activity of GdA, which is responsible for its apoptogenic function. This discovery adds GdA to a select group of soluble immunoregulatory lectins that operate within the feto-placental compartment, the only other members being the galectin family proteins. We also report for the first time that both CD4(+) and CD8(+) T cell subsets are equally susceptible to inhibition with GdA, mediated by its novel lectin activity. We demonstrate that GdA selectively recognizes complex-type N-linked glycans on T cell surface glycoproteins, and propose that the galectin-1 glycoprotein receptor CD7 maybe a novel target for GdA on T cells. This study, for the first time, links the lectin activity of GdA to its biological function.
    Molecular Immunology 09/2009; 46(16):3411-9. DOI:10.1016/j.molimm.2009.07.013 · 2.97 Impact Factor
Show more