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Free Content Small changes in lymphocyte development and activation in mice through tissue-specific alteration of heparan sulphate

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We have examined the role of heparan sulphate in lymphocyte development and activation in mice by conditionally deleting the genes encoding the heparan sulphate biosynthetic enzymes N-deacetylase/N-sulphotransferase-1 and -2 (Ndst1 and Ndst2) and glucuronic acid/N-acetylglucosamine co-polymerase-1 (Ext1) in T cells and B cells, respectively. Ndst1 and Ndst2 are the only Ndst isoforms in T cells. In T-cell Ndst-deficient mice there were normal ratios of CD4+/CD8+ cells in the blood, spleen and thymus, indicating no dramatic effect on development. However, Ndst-deficient T cells were hyperresponsive to low-level activation, suggesting that cell surface heparan sulphate plays a role in T-cell proliferation. The hyperresponsive state correlated with a decrease in cell surface heparan sulphate that occurs in response to activation in wild-type cells. There was a slight change in the number of developing B cells in B-cell Ext1-deficient mice, but the alteration did not cause a change in antibody production. These findings demonstrate that cell surface heparan sulphate may not play a crucial role in lymphocyte development, but can modulate the sensitivity of T cells to activation.
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Keywords: heparan sulphate; lymphocyte; proteoglycan

Document Type: Research Article

Affiliations: 1: Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA 2: Cancer Center, Burnham Institute for Medical Research, La Jolla, CA, USA 3: Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA 4: Institute of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, and Department of Immunology and Transfusion Medicine, St Olav University Hospital, Trondheim, Norway

Publication date: November 1, 2008

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