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

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Abstract
Core 2 β‐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 Lex. 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.