T cell apoptosis at the maternal–fetal interface in early human pregnancy, involvement of galectin-1

Abstract

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 maternalfetal 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 immuneprivileged environment at the maternal-fetal interface.maternal-fetal tolerance ͉ NK cells ͉ lectin ͉ decidua

Adaptive Immune Responses During Pregnancy

“…Gal-1 is known to define autoimmunity, 70 inflammatory neurodegeneration, 71 cardiac inflammation, 72 and tumor escape. 73 74 and recent data confirm that it is not only expressed by the placenta itself 75 but also in uterine NK cells, 76 tolerogenic DCs, 55 and recent data show its importance when expressed in uterine MCs. 58 Pregnancies of Gal-1-deficient mice were first described as normal as the number of born embryos was apparently unaffected by this mutation.…”

Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells

“…36 Decidual NK cells may also use galectin-1 to negatively regulate decidual T cells. 37 Accordingly, it has been demonstrated recently that galectin-1 has an essential function in the generation of tolerogenic DC. 38 Here, we report that galectin-1 is highly expressed in MSCs; it is located intracellularly but is also released by MSCs in high amounts.…”

“…Galectin-1 plays an important role in fetomaternal tolerance and in the human thymus during negative and positive selection of T cells. 36,37,40 Therapeutic administration of galectin-1 in mouse models was effective in several autoimmune diseases. 27 Similarly, GVHD was ameliorated by galectin-1 in a mouse model.…”

Szolubilis és sejteredetű galektin-1 által kiváltott T sejt apoptózis mechanizmusa; egy összehasonlító tanulmány a galektin-1 fiziológiás hatásának meghatározására

“…Az immunrendszer számos sejtje, így az aktivált T és B sejtek (Blaser et al 1998;Zuñiga et al 2001), az aktivált makrofágok (Rabinovich et al 1998), a CD4 + CD25 + regulátor Tsejtek (Treg) és természetes ölő sejtek (Natural killer, NK sejtek) Gal-1-et termelnek (Garín et al 2007;Kopcow et al 2008). A Gal-1 expresszió nagymértékű az immunprivilégizált szövetek sejtjeiben, mint amilyen a placenta (Blois et al 2007), testis (Dettin et al 2003), retina (Ishida et al 2003).…”

“…A monocyták termelte Gal-1 segíti a sejtek migrációját és szerepe játszik a monocyták kemotaxisában (Malik et al 2009). A deciduális NK sejtek Gal-1 termelésükkel hozzájárulnak a méhlepény immunprivilégizált környezetének kialakításához és ezzel a terhesség fenntartásához is (Kopcow et al 2008;Karimi & Arck 2010). A Treg sejteknek kulcsszerepe van az autoimmun betegségek megelőzésében, a perifériás T sejtek toleranciájának kialakításában.…”