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