The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis.
T lymphocyte activation evokes distinct changes in cell surface O-glycans. CD8+ T cells undergo an elimination of sialic acid on core 1 O-glycans and an induction of core 2 O-glycans until either apoptotic death or differentiation into memory cells. We find that the ST3Gal-I sialyltransferase is required for core 1 O-glycan sialylation and its deficiency induces core 2 O-glycan biosynthesis. Apoptosis ensues with the loss of peripheral CD8+ T cells in the absence of immune stimulation. Cell surface ligation of the ST3Gal-I substrate CD43 recapitulates this phenotype by a caspase 3-independent mechanism. Control of core 1 O-glycan sialylation in T lymphocytes by ST3Gal-I comprises a homeostatic mechanism that eliminates CD8+ T cells by apoptosis while facilitating the production of viable CD8+ memory T cells.
Priatel
J J
JJ
Howard Hughes Medical Institute, the Glycobiology Research and Training Center, and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
Chui
D
D
Hiraoka
N
N
Simmons
C J
CJ
Richardson
K B
KB
Page
D M
DM
Fukuda
M
M
Varki
N M
NM
Marth
J D
JD
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006706:Homeostasis; D051917:Leukosialin; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011134:Polysaccharides / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D015703:Antigens, CD; D061945:Caspase Inhibitors; D006023:Glycoproteins; D051917:Leukosialin; D011134:Polysaccharides; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D012799:Sialyltransferases; D020170:Caspase 1; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase