Expression of a specific glycosyltransferase enzyme regulates T cell deathmediated by galectin-1

Galectin-1 induces apoptosis of immature thymocytes and activated T cells, suggesting that galectin-1 regulates cell death in the thymus during select ion and in the periphery following an immune response. Although it is known that galectin-1 recognizes lactosamine (Gal-GlcNAc) as a minimal ligand, t his disaccharide is ubiquitously expressed on a variety of cell surface gly coproteins. Thus, susceptibility to galectin-1 may be regulated by the pres entation of lactosamine on specific oligosaccharide structures created by s pecific glycosyltransferase enzymes. The core 2 beta-1,6-N-acetylglucosamin yltransferase (core 2 GnT) creates a branched structure on O-glycans that c an be elongated to present multiple lactosamine sequences. In the thymus, t he core 2 GnT is expressed in galectin-1-sensitive thymocyte subsets, In th e periphery, an oligosaccharide epitope created by the core 2 GnT is expres sed on galectin-1-sensitive activated T-cells. In this report, we demonstra te that expression of the core 2 GnT was necessary and sufficient for galec tin-1-induced death of murine T cell lines. In addition, over-expression of the core 2 GnT in mice increased the susceptibility of double positive thy mocytes to galectin-1. These data demonstrate that expression of a specific glycosyltransferase can control susceptibility to galectin-1, suggesting t hat developmentally regulated glycosyltransferase expression may be a mecha nism to modulate cell death during T cell development and function.