Expression of a specific glycosyltransferase enzyme regulates T cell death mediated 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 selection and in the periphery following an immune response. Although it is known that galectin-1 recognizes lactosamine (Gal-GlcNAc) as a minimal ligand, this disaccharide is ubiquitously expressed on a variety of cell surface glycoproteins. Thus, susceptibility to galectin-1 may be regulated by the presentation of lactosamine on specific oligosaccharide structures created by specific glycosyltransferase enzymes. The core 2 beta-1, 6-N-acetylglucosaminyltransferase (core 2 GnT) creates a branched structure on O-glycans that can be elongated to present multiple lactosamine sequences. In the thymus, the core 2 GnT is expressed in galectin-1-sensitive thymocyte subsets. In the periphery, an oligosaccharide epitope created by the core 2 GnT is expressed on galectin-1-sensitive activated T-cells. In this report, we demonstrate that expression of the core 2 GnT was necessary and sufficient for galectin-1-induced death of murine T cell lines. In addition, overexpression of the core 2 GnT in mice increased the susceptibility of double positive thymocytes to galectin-1. These data demonstrate that expression of a specific glycosyltransferase can control susceptibility to galectin-1, suggesting that developmentally regulated glycosyltransferase expression may be a mechanism to modulate cell death during T cell development and function.
Galvan
M
M
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90095, USA.
Tsuboi
S
S
Fukuda
M
M
Baum
L G
LG
D000606:Amino Sugars / Q000737:chemistry / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002240:Carbohydrate Sequence; D002460:Cell Line; D037483:Galectin 1; D016695:Glycosyltransferases / Q000378:metabolism* / Q000502:physiology; D006388:Hemagglutinins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology*
D000606:Amino Sugars; D037483:Galectin 1; D006388:Hemagglutinins; D011134:Polysaccharides; C066929:polylactosamine; D016695:Glycosyltransferases