Branched O-linked oligosaccharides ectopically expressed in transgenic mice reduce primary T-cell immune responses

EMBO J. 1997 Nov 3;16(21):6364-73. doi: 10.1093/emboj/16.21.6364.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD*
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cell Adhesion
  • Fibronectins / metabolism
  • Glycosylation
  • Immune Tolerance / physiology*
  • Intercellular Adhesion Molecule-1 / physiology
  • Leukosialin
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Oligosaccharides / chemistry*
  • Organ Specificity
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • Recombinant Fusion Proteins / metabolism
  • Sialoglycoproteins / chemistry
  • Sialoglycoproteins / physiology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Fibronectins
  • Leukosialin
  • Oligosaccharides
  • Recombinant Fusion Proteins
  • Sialoglycoproteins
  • Spn protein, mouse
  • Intercellular Adhesion Molecule-1
  • N-Acetylglucosaminyltransferases
  • beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)