Branched O-linked oligosaccharides ectopically expressed in transgenic mice reduce primary T-cell immune responses.
Core 2 beta-1,6-N-acetylglucosaminyltransferase, C2GnT, is a key enzyme in O-linked oligosaccharide (O-glycan) biosynthesis and the resultant core 2 branch serves as a backbone for additional glycosylation to form oligosaccharide ligands such as sialyl Le(x). Since the expression of C2GnT is highly regulated during T-cell development and increases in pathological conditions such as the Wiskott-Aldrich syndrome, we have generated transgenic mice overexpressing C2GnT in the T-cell lineage. Surprisingly, T lymphocytes in the transgenic mice develop normally, but they exhibit a reduced immune response when assayed by delayed-type hypersensitivity, proliferation upon stimulation and cytokine production. Moreover, T lymphocytes from the transgenic mice adhere much less efficiently to ICAM-1 and fibronectin than do T lymphocytes from non-transgenic mice. These results indicate that overexpression of the core 2 branched O-glycans in T lymphocytes results in reduced immune responses due to impaired cell-cell interaction. Such an impaired immune response may be one of the causes for immunodeficiency in the Wiskott-Aldrich syndrome.
Tsuboi
S
S
Glycobiology Program, La Jolla Cancer Research Center, Burnham Institute, CA 92037, USA.
Fukuda
M
M
D000818:Animals; D015703:Antigens, CD; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D006031:Glycosylation; D007108:Immune Tolerance / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D051917:Leukosialin; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000737:chemistry / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D015703:Antigens, CD; D005353:Fibronectins; D051917:Leukosialin; D009844:Oligosaccharides; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D018799:Intercellular Adhesion Molecule-1; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)